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Staphylococcus aureus

Staphylococcus aureus is a gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often positive for catalase and nitrate reduction and is a facultative anaerobe that can grow without the need for oxygen. Although S. aureus usually acts as a commensal of the human microbiota, it can also become an opportunistic pathogen, being a common cause of skin infections including abscesses, respiratory infections such as sinusitis, and food poisoning. Pathogenic strains often promote infections by producing virulence factors such as potent protein toxins, and the expression of a cell-surface protein that binds and inactivates antibodies. S. aureus is one of the leading pathogens for deaths associated with antimicrobial resistance and the emergence of antibiotic-resistant strains, such as methicillin-resistant S. aureus (MRSA), is a worldwide problem in clinical medicine. Despite much research and development, no vaccine for S. aureus has been approved.

An estimated 21% to 30% of the human population are long-term carriers of S. aureus, which can be found as part of the normal skin microbiota, in the nostrils, and as a normal inhabitant of the lower reproductive tract of females. S. aureus can cause a range of illnesses, from minor skin infections, such as pimples, impetigo, boils, cellulitis, folliculitis, carbuncles, scalded skin syndrome, and abscesses, to life-threatening diseases such as pneumonia, meningitis, osteomyelitis, endocarditis, toxic shock syndrome, bacteremia, and sepsis. It is still one of the five most common causes of hospital-acquired infections and is often the cause of wound infections following surgery. Each year, around 500,000 hospital patients in the United States contract a staphylococcal infection, chiefly by S. aureus. Up to 50,000 deaths each year in the U.S. are linked to staphylococcal infection.

Discovery
In 1880, Alexander Ogston, a Scottish surgeon, discovered that Staphylococcus can cause wound infections after noticing groups of bacteria in pus from a surgical abscess during a procedure he was performing. He named it Staphylococcus after its clustered appearance evident under a microscope. Then, in 1884, German scientist Friedrich Julius Rosenbach identified Staphylococcus aureus, discriminating and separating it from Staphylococcus albus, a related bacterium. In the early 1930s, doctors began to use a more streamlined test to detect the presence of an S. aureus infection by the means of coagulase testing, which enables detection of an enzyme produced by the bacterium. Prior to the 1940s, S. aureus infections were fatal in the majority of patients. However, doctors discovered that the use of penicillin could cure S. aureus infections. Unfortunately, by the end of the 1940s, penicillin resistance became widespread amongst this bacterium population and outbreaks of the resistant strain began to occur.

Evolution
Staphylococcus aureus can be sorted into ten dominant human lineages. There are numerous minor lineages as well, but these are not seen in the population as often. Genomes of bacteria within the same lineage are mostly conserved, with the exception of mobile genetic elements. Mobile genetic elements that are common in S. aureus include bacteriophages, pathogenicity islands, plasmids, transposons, and staphylococcal cassette chromosomes. These elements have enabled S. aureus to continually evolve and gain new traits. There is a great deal of genetic variation within the S. aureus species. A study by Fitzgerald et al. (2001) revealed that approximately 22% of the S. aureus genome is non-coding and thus can differ from bacterium to bacterium. An example of this difference is seen in the species' virulence. Only a few strains of S. aureus are associated with infections in humans. This demonstrates that there is a large range of infectious ability within the species.

It has been proposed that one possible reason for the great deal of heterogeneity within the species could be due to its reliance on heterogeneous infections. This occurs when multiple different types of S. aureus cause an infection within a host. The different strains can secrete different enzymes or bring different antibiotic resistances to the group, increasing its pathogenic ability. Thus, there is a need for a large number of mutations and acquisitions of mobile genetic elements.

Another notable evolutionary process within the S. aureus species is its co-evolution with its human hosts. Over time, this parasitic relationship has led to the bacterium's ability to be carried in the nasopharynx of humans without causing symptoms or infection. This allows it to be passed throughout the human population, increasing its fitness as a species. However, only approximately 50% of the human population are carriers of S. aureus, with 20% as continuous carriers and 30% as intermittent. This leads scientists to believe that there are many factors that determine whether S. aureus is carried asymptomatically in humans, including factors that are specific to an individual person. According to a 1995 study by Hofman et al., these factors may include age, sex, diabetes, and smoking. They also determined some genetic variations in humans that lead to an increased ability for S. aureus to colonize, notably a polymorphism in the glucocorticoid receptor gene that results in larger corticosteroid production. In conclusion, there is evidence that any strain of this bacterium can become invasive, as this is highly dependent upon human factors.

Though S. aureus has quick reproductive and micro-evolutionary rates, there are multiple barriers that prevent evolution with the species. One such barrier is AGR, which is a global accessory gene regulator within the bacteria. This such regulator has been linked to the virulence level of the bacteria. Loss of function mutations within this gene have been found to increase the fitness of the bacterium containing it. Thus, S. aureus must make a trade-off to increase their success as a species, exchanging reduced virulence for increased drug resistance. Another barrier to evolution is the Sau1 Type I restriction modification (RM) system. This system exists to protect the bacterium from foreign DNA by digesting it. Exchange of DNA between the same lineage is not blocked, since they have the same enzymes and the RM system does not recognize the new DNA as foreign, but transfer between different lineages is blocked.

Microbiology
S. aureus (, Greek σταφυλόκοκκος, "grape-cluster berry", Latin aureus, "golden") is a facultative anaerobic, Gram-positive coccal (round) bacterium also known as "golden staph" and "oro staphira". S. aureus is nonmotile and does not form spores. In medical literature, the bacterium is often referred to as S. aureus, Staph aureus or Staph a.. S. aureus appears as staphylococci (grape-like clusters) when viewed through a microscope, and has large, round, golden-yellow colonies, often with hemolysis, when grown on blood agar plates. S. aureus reproduces asexually by binary fission. Complete separation of the daughter cells is mediated by S. aureus autolysin, and in its absence or targeted inhibition, the daughter cells remain attached to one another and appear as clusters.

S. aureus is catalase-positive (meaning it can produce the enzyme catalase). Catalase converts hydrogen peroxide to water and oxygen. Catalase-activity tests are sometimes used to distinguish staphylococci from enterococci and streptococci. Previously, S. aureus was differentiated from other staphylococci by the coagulase test. However, not all S. aureus strains are coagulase-positive and incorrect species identification can impact effective treatment and control measures.

Natural genetic transformation is a reproductive process involving DNA transfer from one bacterium to another through the intervening medium, and the integration of the donor sequence into the recipient genome by homologous recombination. S. aureus was found to be capable of natural genetic transformation, but only at low frequency under the experimental conditions employed. Further studies suggested that the development of competence for natural genetic transformation may be substantially higher under appropriate conditions, yet to be discovered.

Role in health
In humans, S. aureus can be present in the upper respiratory tract, gut mucosa, and skin as a member of the normal microbiota. However, because S. aureus can cause disease under certain host and environmental conditions, it is characterized as a "pathobiont".

Role in disease

While S. aureus usually acts as a commensal bacterium, asymptomatically colonizing about 30% of the human population, it can sometimes cause disease. In particular, S. aureus is one of the most common causes of bacteremia and infective endocarditis. Additionally, it can cause various skin and soft-tissue infections, particularly when skin or mucosal barriers have been breached.

S. aureus infections can spread through contact with pus from an infected wound, skin-to-skin contact with an infected person, and contact with objects used by an infected person such as towels, sheets, clothing, or athletic equipment. Joint replacements put a person at particular risk of septic arthritis, staphylococcal endocarditis (infection of the heart valves), and pneumonia.

S. aureus is a significant cause of chronic biofilm infections on medical implants, and the repressor of toxins is part of the infection pathway.

S. aureus can lay dormant in the body for years undetected. Once symptoms begin to show, the host is contagious for another two weeks, and the overall illness lasts a few weeks. If untreated, though, the disease can be deadly. Deeply penetrating S. aureus infections can be severe.

Skin infections
Skin infections are the most common form of S. aureus infection. This can manifest in various ways, including small benign boils, folliculitis, impetigo, cellulitis, and more severe, invasive soft-tissue infections.

S. aureus is extremely prevalent in persons with atopic dermatitis, more commonly known as eczema. It is mostly found in fertile, active places, including the armpits, hair, and scalp. Large pimples that appear in those areas may exacerbate the infection if lacerated. This can lead to staphylococcal scalded skin syndrome, a severe form of which can be seen in newborns.

The presence of S. aureus in persons with atopic dermatitis is not an indication to treat with oral antibiotics, as evidence has not shown this to give benefit to the patient. However, topical antibiotics combined with corticosteroids have been found to improve the condition. Colonization of S. aureus drives inflammation of atopic dermatitis; S. aureus is believed to exploit defects in the skin barrier of persons with atopic dermatitis, triggering cytokine expression and therefore exacerbating symptoms.

Food poisoning
S. aureus is also responsible for food poisoning and achieves this by generating toxins in the food, which is then ingested. Its incubation period lasts one to six hours, with the illness itself lasting from 30 minutes to 3 days. Preventive measures one can take to help prevent the spread of the disease include washing hands thoroughly with soap and water before preparing food. The Centers for Disease Control and Prevention recommends staying away from any food if ill, and wearing gloves if any open wounds occur on hands or wrists while preparing food. If storing food for longer than 2 hours, it is recommended to keep the food below 4.4 or above 60 °C (below 40 or above 140 °F).

Bone and joint infections
S. aureus is a common cause of major bone and joint infections, including osteomyelitis, septic arthritis, and infections following joint replacement surgeries.

Bacteremia
S. aureus is a leading cause of bloodstream infections throughout much of the industrialized world. Infection is generally associated with breaks in the skin or mucosal membranes due to surgery, injury, or use of intravascular devices such as cannulas, hemodialysis machines, or hypodermic needles. Once the bacteria have entered the bloodstream, they can infect various organs, causing infective endocarditis, septic arthritis, and osteomyelitis. This disease is particularly prevalent and severe in the very young and very old.

Without antibiotic treatment, S. aureus bacteremia has a case fatality rate around 80%. With antibiotic treatment, case fatality rates range from 15% to 50% depending on the age and health of the patient, as well as the antibiotic resistance of the S. aureus strain.

Medical implant infections
S. aureus is often found in biofilms formed on medical devices implanted in the body or on human tissue. It is commonly found with another pathogen, Candida albicans, forming multispecies biofilms. The latter is suspected to help S. aureus penetrate human tissue. A higher mortality is linked with multispecies biofilms.

S. aureus biofilm is the predominant cause of orthopedic implant-related infections, but is also found on cardiac implants, vascular grafts, various catheters, and cosmetic surgical implants. After implantation, the surface of these devices becomes coated with host proteins, which provide a rich surface for bacterial attachment and biofilm formation. Once the device becomes infected, it must be completely removed, since S. aureus biofilm cannot be destroyed by antibiotic treatments.

Current therapy for S. aureus biofilm-mediated infections involves surgical removal of the infected device followed by antibiotic treatment. Conventional antibiotic treatment alone is not effective in eradicating such infections. An alternative to postsurgical antibiotic treatment is using antibiotic-loaded, dissolvable calcium sulfate beads, which are implanted with the medical device. These beads can release high doses of antibiotics at the desired site to prevent the initial infection.

Novel treatments for S. aureus biofilm involving nano silver particles, bacteriophages, and plant-derived antibiotic agents are being studied. These agents have shown inhibitory effects against S. aureus embedded in biofilms. A class of enzymes have been found to have biofilm matrix-degrading ability, thus may be used as biofilm dispersal agents in combination with antibiotics.

Animal infections
S. aureus can survive on dogs, cats, and horses, and can cause bumblefoot in chickens. Some believe health-care workers' dogs should be considered a significant source of antibiotic-resistant S. aureus, especially in times of outbreak. In a 2008 study by Boost, O'Donoghue, and James, it was found that just about 90% of S. aureus colonized within pet dogs presented as resistant to at least one antibiotic. The nasal region has been implicated as the most important site of transfer between dogs and humans.

S. aureus is one of the causal agents of mastitis in dairy cows. Its large polysaccharide capsule protects the organism from recognition by the cow's immune defenses.

Enzymes
S. aureus produces various enzymes such as coagulase (bound and free coagulases) which facilitates the conversion of fibrinogen to fibrin to cause clots which is important in skin infections. Hyaluronidase (also known as spreading factor) breaks down hyaluronic acid and helps in spreading it. Deoxyribonuclease, which breaks down the DNA, protects S. aureus from neutrophil extracellular trap-mediated killing. S. aureus also produces lipase to digest lipids, staphylokinase to dissolve fibrin and aid in spread, and beta-lactamase for drug resistance.

Toxins
Depending on the strain, S. aureus is capable of secreting several exotoxins, which can be categorized into three groups. Many of these toxins are associated with specific diseases.

 * Superantigens
 * Antigens known as superantigens can induce toxic shock syndrome (TSS). This group comprises 25 staphylococcal enterotoxins (SEs) which have been identified to date and named alphabetically (SEA - SEZ), including enterotoxin type B as well as the toxic shock syndrome toxin TSST-1 which causes TSS associated with tampon use. Toxic shock syndrome is characterized by fever, erythematous rash, low blood pressure, shock, multiple organ failure, and skin peeling.  Lack of antibody to TSST-1 plays a part in the pathogenesis of TSS. Other strains of S. aureus can produce an enterotoxin that is the causative agent of a type of gastroenteritis. This form of gastroenteritis is self-limiting, characterized by vomiting and diarrhea 1–6 hours after ingestion of the toxin, with recovery in 8 to 24 hours. Symptoms include nausea, vomiting, diarrhea, and major abdominal pain.

 * Exfoliative toxins

 * Exfoliative toxins are exotoxins implicated in the disease staphylococcal scalded skin syndrome (SSSS), which occurs most commonly in infants and young children. It also may occur as epidemics in hospital nurseries. The protease activity of the exfoliative toxins causes peeling of the skin observed with SSSS.

 * Other toxins
 * Staphylococcal toxins that act on cell membranes include alpha toxin, beta toxin, delta toxin, and several bicomponent toxins. Strains of S. aureus can host phages, such as the prophage Φ-PVL that produces Panton-Valentine leukocidin (PVL), to increase virulence. The bicomponent toxin PVL is associated with severe necrotizing pneumonia in children. The genes encoding the components of PVL are encoded on a bacteriophage found in community-associated MRSA strains.

Type VII Secretion system
A secretion system is a highly specialised multi-protein unit that is embedded in the cell envelope with the function of translocating effector proteins from inside of the cell to the extracellular space or into a target host cytosol. The exact structure and function of T7SS is yet to be fully elucidated. Currently, four proteins are known components of S. aureus type VII secretion system; EssC is a large integral membrane ATPase - which most likely powers the secretion systems and has been hypothesised forming part of the translocation channel. The other proteins are EsaA, EssB, EssA, that are membrane proteins that function alongside EssC to mediate protein secretion. The exact mechanism of how substrates reach the cell surface is unknown, as is the interaction of the three membrane proteins with each other and EssC.

T7 dependent effector proteins

EsaD is DNA endonuclease toxin secreted by S. aureus, has been shown to inhibit growth of competitor S. aureus strain in vitro. EsaD is cosecreted with chaperone EsaE, which stabilises EsaD structure and brings EsaD to EssC for secretion. Strains that produce EsaD also co-produce EsaG, a cytoplasmic anti-toxin that protects the producer strain from EsaD's toxicity.

TspA is another toxin that mediates intraspecies competition. It is a bacteriostatic toxin that has a membrane depolarising activity facilitated by its C-terminal domain. Tsai is a transmembrane protein that confers immunity to the producer strain of TspA, as well as the attacked strains. There is genetic variability of the C-terminal domain of TspA therefore, it seems like the strains may produce different TspA variants to increase competitiveness.

Toxins that play a role in intraspecies competition confers an advantage by promoting successful colonisation in polymicrobial communities such as the nasopharynx and lung by outcompeting lesser strains.

There are also T7 effector proteins that play role a in pathogenesis, for example mutational studies of S. aureus have suggested that EsxB and EsxC contribute to persistent infection in a murine abscess model.

EsxX has been implicated in neutrophil lysis, therefore suggested as contributing to the evasion of host immune system. Deletion of essX in S. aureus resulted in significantly reduced resistance to neutrophils and reduced virulence in murine skin and blood infection models.

Altogether, T7SS and known secreted effector proteins are a strategy of pathogenesis by improving fitness against competitor S. aureus species as well as increased virulence via evading the innate immune system and optimising persistent infections.

Small RNA
The list of small RNAs involved in the control of bacterial virulence in S. aureus is growing. This can be facilitated by factors such as increased biofilm formation in the presence of increased levels of such small RNAs. For example, RNAIII, SprD, SprC, RsaE, SprA1, SSR42, ArtR, SprX, and Teg49.

DNA repair
Host neutrophils cause DNA double-strand breaks in S. aureus through the production of reactive oxygen species. For infection of a host to be successful, S. aureus must survive such damages caused by the hosts' defenses. The two protein complex RexAB encoded by S. aureus is employed in the recombinational repair of DNA double-strand breaks.

Strategies for post-transcriptional regulation by 3'untranslated region
Many mRNAs in S. aureus carry three prime untranslated regions (3'UTR) longer than 100 nucleotides, which may potentially have a regulatory function.

Further investigation of icaR mRNA (mRNA coding for the repressor of the main expolysaccharidic compound of the bacteria biofilm matrix) demonstrated that the 3'UTR binding to the 5' UTR can interfere with the translation initiation complex and generate a double stranded substrate for RNase III. The interaction is between the UCCCCUG motif in the 3'UTR and the Shine-Dalagarno region at the 5'UTR. Deletion of the motif resulted in IcaR repressor accumulation and inhibition of biofilm development. The biofilm formation is the main cause of Staphylococcus implant infections.

Biofilm
Biofilms are groups of microorganisms, such as bacteria, that attach to each other and grow on wet surfaces. The S. aureus biofilm is embedded in a glycocalyx slime layer and can consist of teichoic acids, host proteins, extracellular DNA (eDNA) and sometimes polysaccharide intercellular antigen (PIA). S. aureus biofilms are important in disease pathogenesis, as they can contribute to antibiotic resistance and immune system evasion. S. aureus biofilm has high resistance to antibiotic treatments and host immune response. One hypothesis for explaining this is that the biofilm matrix protects the embedded cells by acting as a barrier to prevent antibiotic penetration. However, the biofilm matrix is composed with many water channels, so this hypothesis is becoming increasingly less likely, but a biofilm matrix possibly contains antibiotic‐degrading enzymes such as β-lactamases, which can prevent antibiotic penetration. Another hypothesis is that the conditions in the biofilm matrix favor the formation of persister cells, which are highly antibiotic-resistant, dormant bacterial cells. S. aureus biofilms also have high resistance to host immune response. Though the exact mechanism of resistance is unknown, S. aureus biofilms have increased growth under the presence of cytokines produced by the host immune response. Host antibodies are less effective for S. aureus biofilm due to the heterogeneous antigen distribution, where an antigen may be present in some areas of the biofilm, but completely absent from other areas.

Studies in biofilm development have shown to be related to changes in gene expression. There are specific genes that were found to be crucial in the different biofilm growth stages. Two of these genes include rocD and gudB, which encode for the enzyme's ornithine-oxo-acid transaminase and glutamate dehydrogenase, which are important for amino acid metabolism. Studies have shown biofilm development rely on amino acids glutamine and glutamate for proper metabolic functions.

Other immunoevasive strategies

 * Protein A

Protein A is anchored to staphylococcal peptidoglycan pentaglycine bridges (chains of five glycine residues) by the transpeptidase sortase A. Protein A, an IgG-binding protein, binds to the Fc region of an antibody. In fact, studies involving mutation of genes coding for protein A resulted in a lowered virulence of S. aureus as measured by survival in blood, which has led to speculation that protein A-contributed virulence requires binding of antibody Fc regions.

Protein A in various recombinant forms has been used for decades to bind and purify a wide range of antibodies by immunoaffinity chromatography. Transpeptidases, such as the sortases responsible for anchoring factors like protein A to the staphylococcal peptidoglycan, are being studied in hopes of developing new antibiotics to target MRSA infections.

 * Staphylococcal pigments

Some strains of S. aureus are capable of producing staphyloxanthin — a golden-coloured carotenoid pigment. This pigment acts as a virulence factor, primarily by being a bacterial antioxidant which helps the microbe evade the reactive oxygen species which the host immune system uses to kill pathogens.

Mutant strains of S. aureus modified to lack staphyloxanthin are less likely to survive incubation with an oxidizing chemical, such as hydrogen peroxide, than pigmented strains. Mutant colonies are quickly killed when exposed to human neutrophils, while many of the pigmented colonies survive. In mice, the pigmented strains cause lingering abscesses when inoculated into wounds, whereas wounds infected with the unpigmented strains quickly heal.

These tests suggest the Staphylococcus strains use staphyloxanthin as a defence against the normal human immune system. Drugs designed to inhibit the production of staphyloxanthin may weaken the bacterium and renew its susceptibility to antibiotics. In fact, because of similarities in the pathways for biosynthesis of staphyloxanthin and human cholesterol, a drug developed in the context of cholesterol-lowering therapy was shown to block S. aureus pigmentation and disease progression in a mouse infection model.

Classical diagnosis

Depending upon the type of infection present, an appropriate specimen is obtained accordingly and sent to the laboratory for definitive identification by using biochemical or enzyme-based tests. A Gram stain is first performed to guide the way, which should show typical Gram-positive bacteria, cocci, in clusters. Second, the isolate is cultured on mannitol salt agar, which is a selective medium with 7.5% NaCl that allows S. aureus to grow, producing yellow-colored colonies as a result of mannitol fermentation and subsequent drop in the medium's pH.

Furthermore, for differentiation on the species level, catalase (positive for all Staphylococcus species), coagulase (fibrin clot formation, positive for S. aureus), DNAse (zone of clearance on DNase agar), lipase (a yellow color and rancid odor smell), and phosphatase (a pink color) tests are all done. For staphylococcal food poisoning, phage typing can be performed to determine whether the staphylococci recovered from the food were the source of infection.

Rapid diagnosis and typing
Diagnostic microbiology laboratories and reference laboratories are key for identifying outbreaks and new strains of S. aureus. Recent genetic advances have enabled reliable and rapid techniques for the identification and characterization of clinical isolates of S. aureus in real time. These tools support infection control strategies to limit bacterial spread and ensure the appropriate use of antibiotics. Quantitative PCR is increasingly being used to identify outbreaks of infection.

When observing the evolvement of S. aureus and its ability to adapt to each modified antibiotic, two basic methods known as "band-based" or "sequence-based" are employed. Keeping these two methods in mind, other methods such as multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE), bacteriophage typing, spa locus typing, and SCCmec typing are often conducted more than others. With these methods, it can be determined where strains of MRSA originated and also where they are currently.

With MLST, this technique of typing uses fragments of several housekeeping genes known as aroE, glpF, gmk, pta, tip, and yqiL. These sequences are then assigned a number which give to a string of several numbers that serve as the allelic profile. Although this is a common method, a limitation about this method is the maintenance of the microarray which detects newly allelic profiles, making it a costly and time-consuming experiment.

With PFGE, a method which is still very much used dating back to its first success in 1980s, remains capable of helping differentiate MRSA isolates. To accomplish this, the technique uses multiple gel electrophoresis, along with a voltage gradient to display clear resolutions of molecules. The S. aureus fragments then transition down the gel, producing specific band patterns that are later compared with other isolates in hopes of identifying related strains. Limitations of the method include practical difficulties with uniform band patterns and PFGE sensitivity as a whole.

Spa locus typing is also considered a popular technique that uses a single locus zone in a polymorphic region of S. aureus to distinguish any form of mutations. Although this technique is often inexpensive and less time-consuming, the chance of losing discriminatory power making it hard to differentiate between MLST clonal complexes exemplifies a crucial limitation.

Treatment
For susceptible strains, the treatment of choice for S. aureus infection is penicillin. An antibiotic derived from some Penicillium fungal species, penicillin inhibits the formation of peptidoglycan cross-linkages that provide the rigidity and strength in a bacterial cell wall. The four-membered β-lactam ring of penicillin is bound to enzyme DD-transpeptidase, an enzyme that when functional, cross-links chains of peptidoglycan that form bacterial cell walls. The binding of β-lactam to DD-transpeptidase inhibits the enzyme's functionality and it can no longer catalyze the formation of the cross-links. As a result, cell wall formation and degradation are imbalanced, thus resulting in cell death. In most countries, however, penicillin resistance is extremely common (>90%), and first-line therapy is most commonly a penicillinase-resistant β-lactam antibiotic (for example, oxacillin or flucloxacillin, both of which have the same mechanism of action as penicillin) or vancomycin, depending on local resistance patterns. Combination therapy with gentamicin may be used to treat serious infections, such as endocarditis, but its use is controversial because of the high risk of damage to the kidneys. The duration of treatment depends on the site of infection and on severity. Adjunctive rifampicin has been historically used in the management of S aureus bacteraemia, but randomised controlled trial evidence has shown this to be of no overall benefit over standard antibiotic therapy.

Antibiotic resistance in S. aureus was uncommon when penicillin was first introduced in 1943. Indeed, the original Petri dish on which Alexander Fleming of Imperial College London observed the antibacterial activity of the Penicillium fungus was growing a culture of S. aureus. By 1950, 40% of hospital S. aureus isolates were penicillin-resistant; by 1960, this had risen to 80%.

Methicillin-resistant Staphylococcus aureus (MRSA, often pronounced or ), is one of a number of greatly feared strains of S. aureus which have become resistant to most β-lactam antibiotics. For this reason, vancomycin, a glycopeptide antibiotic, is commonly used to combat MRSA. Vancomycin inhibits the synthesis of peptidoglycan, but unlike β-lactam antibiotics, glycopeptide antibiotics target and bind to amino acids in the cell wall, preventing peptidoglycan cross-linkages from forming. MRSA strains are most often found associated with institutions such as hospitals, but are becoming increasingly prevalent in community-acquired infections.

Minor skin infections can be treated with triple antibiotic ointment. One topical agent that is prescribed is mupirocin, a protein synthesis inhibitor that is produced naturally by Pseudomonas fluorescens and has seen success for treatment of S. aureus nasal carriage.

Antibiotic resistance
S. aureus was found to be the second leading pathogen for deaths associated with antimicrobial resistance in 2019.

Staphylococcal resistance to penicillin is mediated by penicillinase (a form of beta-lactamase) production: an enzyme that cleaves the β-lactam ring of the penicillin molecule, rendering the antibiotic ineffective. Penicillinase-resistant β-lactam antibiotics, such as methicillin, nafcillin, oxacillin, cloxacillin, dicloxacillin, and flucloxacillin are able to resist degradation by staphylococcal penicillinase. Resistance to methicillin is mediated via the mec operon, part of the staphylococcal cassette chromosome mec (SCCmec). SCCmec is a family of mobile genetic elements, which is a major driving force of S. aureus evolution. Resistance is conferred by the mecA gene, which codes for an altered penicillin-binding protein (PBP2a or PBP2') that has a lower affinity for binding β-lactams (penicillins, cephalosporins, and carbapenems). This allows for resistance to all β-lactam antibiotics, and obviates their clinical use during MRSA infections. Studies have explained that this mobile genetic element has been acquired by different lineages in separate gene transfer events, indicating that there is not a common ancestor of differing MRSA strains. Interestingly, one study suggests that MRSA sacrifices virulence, for example, toxin production and invasiveness, for survival and creation of biofilms

Aminoglycoside antibiotics, such as kanamycin, gentamicin, streptomycin, were once effective against staphylococcal infections until strains evolved mechanisms to inhibit the aminoglycosides' action, which occurs via protonated amine and/or hydroxyl interactions with the ribosomal RNA of the bacterial 30S ribosomal subunit. Three main mechanisms of aminoglycoside resistance mechanisms are currently and widely accepted: aminoglycoside modifying enzymes, ribosomal mutations, and active efflux of the drug out of the bacteria.

Aminoglycoside-modifying enzymes inactivate the aminoglycoside by covalently attaching either a phosphate, nucleotide, or acetyl moiety to either the amine or the alcohol key functional group (or both groups) of the antibiotic. This changes the charge or sterically hinders the antibiotic, decreasing its ribosomal binding affinity. In S. aureus, the best-characterized aminoglycoside-modifying enzyme is aminoglycoside adenylyltransferase 4' IA (ANT(4')IA). This enzyme has been solved by X-ray crystallography. The enzyme is able to attach an adenyl moiety to the 4' hydroxyl group of many aminoglycosides, including kanamycin and gentamicin.

Glycopeptide resistance is typically mediated by acquisition of the vanA gene, which originates from the Tn1546 transposon found in a plasmid in enterococci and codes for an enzyme that produces an alternative peptidoglycan to which vancomycin will not bind.

Today, S. aureus has become resistant to many commonly used antibiotics. In the UK, only 2% of all S. aureus isolates are sensitive to penicillin, with a similar picture in the rest of the world. The β-lactamase-resistant penicillins (methicillin, oxacillin, cloxacillin, and flucloxacillin) were developed to treat penicillin-resistant S. aureus, and are still used as first-line treatment. Methicillin was the first antibiotic in this class to be used (it was introduced in 1959), but only two years later, the first case of methicillin-resistant Staphylococcus aureus (MRSA) was reported in England.

Despite this, MRSA generally remained an uncommon finding, even in hospital settings, until the 1990s, when the MRSA prevalence in hospitals exploded, and it is now endemic. Now, methicillin-resistant Staphylococcus aureus (MRSA) is not only a human pathogen causing a variety of infections, such as skin and soft tissue infection (SSTI), pneumonia, and sepsis, but it also can cause disease in animals, known as livestock-associated MRSA (LA-MRSA).

MRSA infections in both the hospital and community setting are commonly treated with non-β-lactam antibiotics, such as clindamycin (a lincosamine) and co-trimoxazole (also commonly known as trimethoprim/sulfamethoxazole). Resistance to these antibiotics has also led to the use of new, broad-spectrum anti-Gram-positive antibiotics, such as linezolid, because of its availability as an oral drug. First-line treatment for serious invasive infections due to MRSA is currently glycopeptide antibiotics (vancomycin and teicoplanin). A number of problems with these antibiotics occur, such as the need for intravenous administration (no oral preparation is available), toxicity, and the need to monitor drug levels regularly by blood tests. Also, glycopeptide antibiotics do not penetrate very well into infected tissues (this is a particular concern with infections of the brain and meninges and in endocarditis). Glycopeptides must not be used to treat methicillin-sensitive S. aureus (MSSA), as outcomes are inferior.

Because of the high level of resistance to penicillins and because of the potential for MRSA to develop resistance to vancomycin, the U.S. Centers for Disease Control and Prevention has published guidelines for the appropriate use of vancomycin. In situations where the incidence of MRSA infections is known to be high, the attending physician may choose to use a glycopeptide antibiotic until the identity of the infecting organism is known. After the infection is confirmed to be due to a methicillin-susceptible strain of S. aureus, treatment can be changed to flucloxacillin or even penicillin, as appropriate.

Vancomycin-resistant S. aureus (VRSA) is a strain of S. aureus that has become resistant to the glycopeptides. The first case of vancomycin-intermediate S. aureus (VISA) was reported in Japan in 1996; but the first case of S. aureus truly resistant to glycopeptide antibiotics was only reported in 2002. Three cases of VRSA infection had been reported in the United States as of 2005. At least in part the antimicrobial resistance in S. aureus can be explained by its ability to adapt. Multiple two component signal transduction pathways helps S. aureus to express genes that are required to survive under antimicrobial stress.

Efflux pumps
Among the various mechanisms that MRSA acquires to elude antibiotic resistance (e.g., drug inactivation, target alteration, reduction of permeability) there is also the overexpression of efflux pumps. Efflux pumps are membrane-integrated proteins that are physiologically needed in the cell for the exportation of xenobiotic compounds. They are divided into six families, each of which has a different structure, function, and transport of energy. The main efflux pumps of S. aureus are the MFS (Major Facilitator Superfamily) which includes the MdeA pump as well as the NorA pump and the MATE (Multidrug and Toxin Extrusion) to which it belongs the MepA pump. For transport, these families use an electrochemical potential and an ion concentration gradient, while the ATP-binding cassette (ABC) family acquires its energy from the hydrolysis of ATP.

These pumps are overexpressed by MDR S. aureus (Multidrug resistant S. aureus) and the result is an excessive expulsion of the antibiotic outside the cell, which makes its action ineffective. Efflux pumps also contribute significantly to the development of impenetrable biofilms.

By directly modulating efflux pumps' activity or decreasing their expression, it may be possible to modify the resistant phenotype and restore the effectiveness of existing antibiotics.

Carriage
About 33% of the U.S. population are carriers of S. aureus and about 2% carry MRSA. Even healthcare providers can be MRSA colonizers.

The carriage of S. aureus is an important source of hospital-acquired infection (also called nosocomial) and community-acquired MRSA. Although S. aureus can be present on the skin of the host, a large proportion of its carriage is through the anterior nares of the nasal passages and can further be present in the ears. The ability of the nasal passages to harbour S. aureus results from a combination of a weakened or defective host immunity and the bacterium's ability to evade host innate immunity. Nasal carriage is also implicated in the occurrence of staph infections.

Infection control
Spread of S. aureus (including MRSA) generally is through human-to-human contact, although recently some veterinarians have discovered the infection can be spread through pets, with environmental contamination thought to play a relatively less important part. Emphasis on basic hand washing techniques are, therefore, effective in preventing its transmission. The use of disposable aprons and gloves by staff reduces skin-to-skin contact, so further reduces the risk of transmission.

Recently, myriad cases of S. aureus have been reported in hospitals across America. Transmission of the pathogen is facilitated in medical settings where healthcare worker hygiene is insufficient. S. aureus is an incredibly hardy bacterium, as was shown in a study where it survived on polyester for just under three months; polyester is the main material used in hospital privacy curtains.

The bacteria are transported on the hands of healthcare workers, who may pick them up from a seemingly healthy patient carrying a benign or commensal strain of S. aureus, and then pass it on to the next patient being treated. Introduction of the bacteria into the bloodstream can lead to various complications, including endocarditis, meningitis, and, if it is widespread, sepsis.

Ethanol has proven to be an effective topical sanitizer against MRSA. Quaternary ammonium can be used in conjunction with ethanol to increase the duration of the sanitizing action. The prevention of nosocomial infections involves routine and terminal cleaning. Nonflammable alcohol vapor in NAV- systems have an advantage, as they do not attack metals or plastics used in medical environments, and do not contribute to antibacterial resistance.

An important and previously unrecognized means of community-associated MRSA colonization and transmission is during sexual contact.

S. aureus is killed in one minute at 78 °C and in ten minutes at 64 °C but is resistant to freezing.

Certain strains of S. aureus have been described as being resistant to chlorine disinfection.

The use of mupirocin ointment can reduce the rate of infections due to nasal carriage of S. aureus. There is limited evidence that nasal decontamination of S. aureus using antibiotics or antiseptics can reduce the rates of surgical site infections.

Research
As of 2021, no approved vaccine exists against S. aureus. Early clinical trials have been conducted for several vaccines candidates such as Nabi's StaphVax and PentaStaph, Intercell's / Merck's V710, VRi's SA75, and others.

While some of these vaccines candidates have shown immune responses, others aggravated an infection by S. aureus. To date, none of these candidates provides protection against a S. aureus infection. The development of Nabi's StaphVax was stopped in 2005 after phase III trials failed. Intercell's first V710 vaccine variant was terminated during phase II/III after higher mortality and morbidity were observed among patients who developed S. aureus infection.

Nabi's enhanced S. aureus vaccines candidate PentaStaph was sold in 2011 to GlaxoSmithKline Biologicals S.A. The current status of PentaStaph is unclear. A WHO document indicates that PentaStaph failed in the phase III trial stage.

In 2010, GlaxoSmithKline started a phase 1 blind study to evaluate its GSK2392103A vaccine. As of 2016, this vaccine is no longer under active development.

Pfizer's S. aureus four-antigen vaccine SA4Ag was granted fast track designation by the U.S. Food and Drug Administration in February 2014. In 2015, Pfizer has commenced a phase 2b trial regarding the SA4Ag vaccine. Phase 1 results published in February 2017 showed a very robust and secure immunogenicity of SA4Ag. The vaccine underwent clinical trial until June 2019, with results published in September 2020, that did not demonstrate a significant reduction in Postoperative Bloodstream Infection after Surgery.

In 2015, Novartis Vaccines and Diagnostics, a former division of Novartis and now part of GlaxoSmithKline, published promising pre-clinical results of their four-component Staphylococcus aureus vaccine, 4C-staph.

In addition to vaccine development, research is being performed to develop alternative treatment options that are effective against antibiotic resistant strains including MRSA. Examples of alternative treatments are phage therapy, antimicrobial peptides and host-directed therapy.

Standard strains
A number of standard strains of S. aureus (called "type cultures") are used in research and in laboratory testing, such as:

title: Staphylococcus aureus


text:
Carson City, Michigan

Carson City is a city in Montcalm County of the U.S. state of Michigan. The population was 1,120 at the 2020 census.

History
Carson City was first platted in 1866 on land owned by R. M. Abbott, Delia Miner, and Hiram T. Sherman, and recorded in 1871. The first lot was sold to Thomas Scott and two nephews, John and Thomas LaDue, in 1867. With the corporate name Scott & LaDue, they built a sawmill in 1868 and a grist mill in 1870. The post office from North Shade in Gratiot County was transferred to this location on August 3, 1868, with Hiram T. Sherman as the first postmaster. The name "Carson City" was given to the post office by Thomas Scott, who had been in Carson City, Nevada, during the gold and silver mining boom days. Carson City incorporated as a village in 1887 and as a city in 1960. The first mayor of Carson City was John T. Hallett.

Geography
Carson City is in southeastern Montcalm County, bordered to the north, west, and south by Bloomer Township and to the east by North Shade Township in Gratiot County. State highway M-57 runs through the city as Main Street, leading west 20 mi to Greenville and east 37 mi to Chesaning. Stanton, the Montcalm county seat, is 20 mi by road to the northwest.

According to the U.S. Census Bureau, Carson City has a total area of 1.17 sqmi, of which 1.14 sqmi are land and 0.03 sqmi, or 2.47%, are water. Fish Creek, a tributary of the Maple River and part of the Grand River watershed leading to Lake Michigan, flows southward along the western edge of the city.

2010 census
As of the census of 2010, there were 1,093 people, 451 households, and 271 families residing in the city. The population density was 1051.0 PD/sqmi. There were 521 housing units at an average density of 501.0 /sqmi. The racial makeup of the city was 96.7% White, 0.4% African American, 0.3% Native American, 0.5% Asian, 0.7% from other races, and 1.4% from two or more races. Hispanic or Latino of any race were 4.2% of the population.

There were 451 households, of which 30.4% had children under the age of 18 living with them, 40.6% were married couples living together, 14.4% had a female householder with no husband present, 5.1% had a male householder with no wife present, and 39.9% were non-families. 35.7% of all households were made up of individuals, and 17.1% had someone living alone who was 65 years of age or older. The average household size was 2.27 and the average family size was 2.93.

The median age in the city was 41.8 years. 24.4% of residents were under the age of 18; 9.2% were between the ages of 18 and 24; 20.7% were from 25 to 44; 21.8% were from 45 to 64; and 24% were 65 years of age or older. The gender makeup of the city was 43.7% male and 56.3% female.

2000 census
As of the census of 2000, there were 1,190 people, 496 households, and 312 families residing in the city. The population density was 1,670.8 PD/sqmi. There were 532 housing units at an average density of 746.9 /sqmi. The racial makeup of the city was 95.04% White, 0.50% African American, 0.17% Native American, 0.34% Asian, 2.10% from other races, and 1.85% from two or more races. Hispanic or Latino of any race were 4.54% of the population.

There were 496 households, out of which 32.5% had children under the age of 18 living with them, 44.6% were married couples living together, 13.1% had a female householder with no husband present, and 36.9% were non-families. 32.3% of all households were made up of individuals, and 15.7% had someone living alone who was 65 years of age or older. The average household size was 2.39 and the average family size was 3.01.

In the city, the population was spread out, with 28.4% under the age of 18, 7.9% from 18 to 24, 27.1% from 25 to 44, 21.4% from 45 to 64, and 15.1% who were 65 years of age or older. The median age was 36 years. For every 100 females, there were 82.0 males. For every 100 females age 18 and over, there were 75.3 males.

The median income for a household in the city was $32,500, and the median income for a family was $41,477. Males had a median income of $31,442 versus $28,472 for females. The per capita income for the city was $19,178. About 11.7% of families and 15.2% of the population were below the poverty line, including 19.2% of those under age 18 and 12.9% of those age 65 or over.

Amenities
The Carson City post office, with ZIP code 48811, serves most of Bloomer Township and southern portions of Crystal Township in Montcalm County and the western portions of North Shade Township and southwestern New Haven Township in Gratiot County.

The nearest airport is Mayes Airport, a privately owned airport located about 4.3 mi away.(closed)

Education
The city is served by the Carson City-Crystal Area Schools, which operates a lower elementary school, a combined upper elementary-middle school and a high school. Its mascot is the eagle.

Notable people

 * Orson Baldwin (1881–1942), Major League Baseball player for the St. Louis Cardinals
 * Daniel Henney (b. 1979), actor and model
 * Bill Knot (1940–2014), poet
 * William C. Lawe (1910–1942), United States Navy sailor during World War II and Distinguished Flying Cross recipient

license: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/4.0/

title: Carson City, Michigan


text:
Cato Township, Michigan

Cato Township is a civil township of Montcalm County in the U.S. state of Michigan. The population was 2,898 at the 2020 census.

History
Cato Township was established in 1857.

Communities

 * Bass Beach was a resort village platted by George Whitcomb and his wife in 1889.
 * Lakeview is a village in the northern part of the township. The Lakeview ZIP Code (48850) serves all but the southeast corner of the township.

Geography
The township is in northern Montcalm County and is bordered to the north by Mecosta County. State highway M-46 crosses the center of the township, leading east to Edmore and west to US 131 in Reynolds Township. M-91 has its northern terminus in Cato Township and leads south to Greenville.

According to the U.S. Census Bureau, the Cato Township has a total area of 36.0 sqmi, of which 35.2 sqmi are land and 0.85 sqmi, or 2.37%, are water. The township is drained to the west by Tamarack Creek, a tributary of the Little Muskegon River, and to the east by tributaries of the Flat River, a south-flowing tributary of the Grand River. Tamarack Lake is in the northern part of the township, partly within the village of Lakeview, and Townline Lake is in the northeast part of the township on the border with Belvidere Township.

Demographics
As of the census of 2000, there were 2,920 people, 1,073 households, and 789 families residing in the township. The population density was 82.8 PD/sqmi. There were 1,307 housing units at an average density of 37.1 /sqmi. The racial makeup of the township was 96.71% White, 0.17% African American, 0.41% Native American, 0.27% Asian, 0.07% Pacific Islander, 0.65% from other races, and 1.71% from two or more races. Hispanic or Latino of any race were 2.71% of the population.

There were 1,073 households, out of which 34.6% had children under the age of 18 living with them, 58.3% were married couples living together, 10.9% had a female householder with no husband present, and 26.4% were non-families. 22.2% of all households were made up of individuals, and 11.3% had someone living alone who was 65 years of age or older. The average household size was 2.67 and the average family size was 3.07.

In the township the population was spread out, with 28.8% under the age of 18, 7.6% from 18 to 24, 28.4% from 25 to 44, 19.6% from 45 to 64, and 15.6% who were 65 years of age or older. The median age was 36 years. For every 100 females, there were 92.4 males. For every 100 females age 18 and over, there were 90.4 males.

The median income for a household in the township was $35,919, and the median income for a family was $40,625. Males had a median income of $31,304 versus $22,000 for females. The per capita income for the township was $15,495. About 8.7% of families and 11.4% of the population were below the poverty line, including 13.6% of those under age 18 and 10.8% of those age 65 or over.

title: Cato Township, Michigan


text:
Day Township, Michigan

Day Township is a civil township of Montcalm County in the U.S. state of Michigan. As of the 2020 census, the township population was 1,141.

The Mid Michigan Motorplex, formerly known as the Central Michigan Dragway, is located within the township.

Communities

 * McBride is a village in the township, near the junction of county road 530 (McBrides Road) and county road 571 (Wyman Road). The post office for the village, with ZIP code 48852, is named "McBrides" and provides P.O. box service for the village.
 * Westville is an unincorporated community on the western boundary of the township at 43.35778°N, -85.08361°W, about 2 mi west of McBride and about 4 mi north of Stanton. A post office was established on May 2, 1872, with Eli M. Mallet as the first postmaster. The community was platted and recorded as "Westville" by Daniel West. The post office continued to operate until October 31, 1907.
 * The city of Stanton is situated at the southwest corner of the township and incorporates most of section 31. The Stanton post office, with ZIP code 48888, also serves most of southern Day Township.

Geography
Day Township is in northeastern Montcalm County, bordered to the southwest by the city of Stanton, the county seat. According to the U.S. Census Bureau, the township has a total area of 35.4 sqmi, of which 35.3 sqmi are land and 0.1 sqmi, or 0.24%, are water. The township is drained to the west by tributaries of the Flat River and to the east by tributaries of Fish Creek, which passes through the southeast part of the township. Both waterways are part of the Grand River watershed leading west to Lake Michigan.

Demographics
As of the census of 2000, there were 1,282 people, 461 households, and 366 families residing in the township. The population density was 36.4 PD/sqmi. There were 496 housing units at an average density of 14.1 /sqmi. The racial makeup of the township was 96.49% White, 0.23% African American, 0.62% Native American, 0.16% Asian, 0.08% Pacific Islander, 0.39% from other races, and 2.03% from two or more races. Hispanic or Latino of any race were 2.65% of the population.

There were 461 households, out of which 34.1% had children under the age of 18 living with them, 67.2% were married couples living together, 7.6% had a female householder with no husband present, and 20.6% were non-families. 16.7% of all households were made up of individuals, and 8.9% had someone living alone who was 65 years of age or older. The average household size was 2.78 and the average family size was 3.08.

In the township the population was spread out, with 27.6% under the age of 18, 8.6% from 18 to 24, 27.3% from 25 to 44, 23.6% from 45 to 64, and 12.9% who were 65 years of age or older. The median age was 36 years. For every 100 females, there were 101.6 males. For every 100 females age 18 and over, there were 95.0 males.

The median income for a household in the township was $35,500, and the median income for a family was $42,566. Males had a median income of $30,167 versus $19,348 for females. The per capita income for the township was $16,724. About 8.1% of families and 13.3% of the population were below the poverty line, including 22.5% of those under age 18 and 7.4% of those age 65 or over.

title: Day Township, Michigan


text:
Douglass Township, Michigan

Douglass Township is a civil township of Montcalm County in the U.S. state of Michigan. The population was 2,239 at the 2020 census.

Communities

 * Entrican is a small unincorporated community on the Flat River at 43.35028°N, -85.15361°W.

Geography
The township is in north-central Montcalm County and is bordered to the southeast by the city of Stanton, the county seat. According to the U.S. Census Bureau, the township has a total area of 35.6 sqmi, of which 34.7 sqmi are land and 0.9 sqmi, or 2.57%, are water. Clifford Lake and Dickerson Lake are in the southwest part of the township. The township is drained by the Flat River, a south-flowing tributary of the Grand River.

Demographics
As of the census of 2000, there were 2,377 people, 891 households, and 669 families residing in the township. The population density was 68.0 PD/sqmi. There were 1,116 housing units at an average density of 31.9 /sqmi. The racial makeup of the township was 98.06% White, 0.08% African American, 0.17% Native American, 0.21% Asian, 0.46% from other races, and 1.01% from two or more races. Hispanic or Latino of any race were 2.31% of the population.

There were 891 households, out of which 34.5% had children under the age of 18 living with them, 63.6% were married couples living together, 6.8% had a female householder with no husband present, and 24.9% were non-families. 19.5% of all households were made up of individuals, and 9.4% had someone living alone who was 65 years of age or older. The average household size was 2.66 and the average family size was 3.04.

In the township the population was spread out, with 26.9% under the age of 18, 7.3% from 18 to 24, 27.1% from 25 to 44, 25.7% from 45 to 64, and 13.0% who were 65 years of age or older. The median age was 37 years. For every 100 females, there were 98.2 males. For every 100 females age 18 and over, there were 101.3 males.

The median income for a household in the township was $44,309, and the median income for a family was $47,560. Males had a median income of $32,426 versus $24,375 for females. The per capita income for the township was $17,892. About 2.4% of families and 4.6% of the population were below the poverty line, including 5.0% of those under age 18 and 6.6% of those age 65 or over.

title: Douglass Township, Michigan


text:
Edmore, Michigan

Edmore is a village in Montcalm County of the U.S. state of Michigan. The population was 1,210 at the 2020 census.

History
Edmore was founded and platted by Edwin B. Moore, a real estate man, in 1878, and named with a contraction of his name. A post office was established on July 22, 1878, with Abraham West as the first postmaster. Its station on the Detroit, Lansing and Northern Railroad was called "Edmore Junction". It was incorporated as a village in 1879 with Moore as its first president.

The Edmore post office, with ZIP code 48829, serves most of Home Township as well as portions of Belvidere Township to the west, Douglass Township to the southwest, Day Township to the south, Ferris Township to the southeast, and Rolland Township to the north in Isabella County.

Edmore is close to the site of the finds of the forged Scotford-Soper-Savage relics.

The Edmore meteorite was discovered on a nearby farm in 2018. It had reportedly fallen to earth in the 1930s on another farm and had been used as a doorstop since then.

Geography
Edmore is in northeastern Montcalm County, in the south-central part of Home Township. It is 10 mi by road north-northeast of Stanton, the county seat. According to the U.S. Census Bureau, the village has a total area of 1.52 sqmi, all land.

Highways

 * is a highway that nearly bisects the Lower Peninsula of Michigan latitudinally. The highway leads east 21 mi to St. Louis and west 12 mi to Lakeview.

2010 census
As of the census of 2010, there were 1,201 people, 512 households, and 324 families residing in the village. The population density was 795.4 PD/sqmi. There were 565 housing units at an average density of 374.2 /sqmi. The racial makeup of the village was 94.9% White, 0.5% African American, 0.5% Native American, 0.2% Asian, 0.9% from other races, and 3.0% from two or more races. Hispanic or Latino of any race were 4.1% of the population.

There were 512 households, of which 32.0% had children under the age of 18 living with them, 37.9% were married couples living together, 18.8% had a female householder with no husband present, 6.6% had a male householder with no wife present, and 36.7% were non-families. 31.8% of all households were made up of individuals, and 14% had someone living alone who was 65 years of age or older. The average household size was 2.31 and the average family size was 2.85.

The median age in the village was 38.8 years. 24.6% of residents were under the age of 18; 10.1% were between the ages of 18 and 24; 23.6% were from 25 to 44; 25.1% were from 45 to 64; and 16.6% were 65 years of age or older. The gender makeup of the village was 46.0% male and 54.0% female.

2000 census
As of the census of 2000, there were 1,244 people, 491 households, and 334 families residing in the village. The population density was 875.7 PD/sqmi. There were 524 housing units at an average density of 368.8 /sqmi. The racial makeup of the village was 95.50% White, 0.40% African American, 0.80% Native American, 0.56% from other races, and 2.73% from two or more races. Hispanic or Latino of any race were 2.97% of the population.

There were 491 households, out of which 37.3% had children under the age of 18 living with them, 48.1% were married couples living together, 13.6% had a female householder with no husband present, and 31.8% were non-families. 29.3% of all households were made up of individuals, and 16.1% had someone living alone who was 65 years of age or older. The average household size was 2.49 and the average family size was 3.05.

In the village, the population was spread out, with 29.7% under the age of 18, 9.5% from 18 to 24, 25.7% from 25 to 44, 17.2% from 45 to 64, and 17.9% who were 65 years of age or older. The median age was 34 years. For every 100 females, there were 87.1 males. For every 100 females age 18 and over, there were 81.2 males.

The median income for a household in the village was $24,926, and the median income for a family was $35,391. Males had a median income of $30,156 versus $22,045 for females. The per capita income for the village was $12,853. About 16.8% of families and 20.7% of the population were below the poverty line, including 26.4% of those under age 18 and 11.8% of those age 65 or over.

title: Edmore, Michigan


text:
Eureka Township, Michigan

Eureka Township is a charter township of Montcalm County in the U.S. state of Michigan. The population was 4,211 at the 2020 census, up from 3,959 in 2010.

The township surrounds the city of Greenville, a separate municipality, and the Greenville post office, with ZIP code 48838, serves all of Eureka Township. Eureka Township was established in 1850.

Geography
The township is in southern Montcalm County, bordered to the north by Montcalm Township, to the northeast by Sidney Township, to the east by Fairplain Township, to the south by Ionia County, and to the west by Kent County. The city of Greenville occupies what was originally the northern part of Eureka Township.

State highways M-57 and M-91 cross the township, intersecting in Greenville. M-57 leads east 20 mi to Carson City and west 16 mi to U.S. Route 131 near Edgerton, while M-91 leads south 6 mi to its terminus near Belding and north 19 mi to Lakeview.

According to the U.S. Census Bureau, Eureka Township has a total area of 29.6 sqmi, of which 28.7 sqmi are land and 0.9 sqmi, or 2.89%, are water. The township is drained by the Flat River, which flows through Greenville and across the southeast part of the township, part of the Grand River watershed. Wabasis Creek, a tributary of the Flat River, drains the southwest part of the township.

Demographics
As of the census of 2000, there were 3,271 people, 1,179 households, and 929 families residing in the township. The population density was 110.7 PD/sqmi. There were 1,248 housing units at an average density of 42.2 /sqmi. The racial makeup of the township was 96.36% White, 0.15% African American, 0.55% Native American, 0.43% Asian, 1.35% from other races, and 1.16% from two or more races. Hispanic or Latino of any race were 3.15% of the population.

There were 1,179 households, out of which 37.4% had children under the age of 18 living with them, 68.4% were married couples living together, 6.5% had a female householder with no husband present, and 21.2% were non-families. 17.2% of all households were made up of individuals, and 5.5% had someone living alone who was 65 years of age or older. The average household size was 2.77 and the average family size was 3.09.

In the township the population was spread out, with 27.9% under the age of 18, 7.1% from 18 to 24, 29.5% from 25 to 44, 25.1% from 45 to 64, and 10.4% who were 65 years of age or older. The median age was 37 years. For every 100 females, there were 102.9 males. For every 100 females age 18 and over, there were 102.3 males.

The median income for a household in the township was $50,566, and the median income for a family was $53,380. Males had a median income of $39,919 versus $28,173 for females. The per capita income for the township was $20,223. About 3.2% of families and 5.4% of the population were below the poverty line, including 4.1% of those under age 18 and 9.6% of those age 65 or over.

title: Eureka Township, Michigan


text:
Fairplain Township, Michigan

Fairplain Township is a civil township of Montcalm County in the U.S. state of Michigan. The population was 1,802 at the 2020 census.

Communities

 * Fenwick is an unincorporated community in the southeast part of the township at 43.14917°N, -85.08028°W. The Fenwick post office, with ZIP code 48834, serves the southeastern portion of Fairplain Township as well as portions of surrounding townships. Fenwick was founded in 1872 by B. C. Loree, who named it after his home town, Fenwick, Ontario. A post office opened on April 28, 1873, with James R. Hall as its first postmaster. It was platted and recorded on May 22, 1874, by S. C. Alderman for the proprietors Simon M., Sarah, and David Griswold. 1897 cadastral map of Fenwick, Michigan.jpg

Geography
Fairplain Township is in southern Montcalm County and is bordered to the south by Ionia County. State highway M-57 crosses the central part of the township, leading west to Greenville and east to Carson City.

According to the U.S. Census Bureau, the township has a total area of 36.0 sqmi, of which 35.2 sqmi are land and 0.7 sqmi, or 2.05%, are water. The township is drained by Dickerson Creek, a tributary of the Flat River, except for small areas on the eastern border which drain to Prairie Creek. The Flat River and Prairie Creek are each south-flowing tributaries of the Grand River, flowing to Lake Michigan.

Demographics
As of the census of 2000, there were 1,826 people, 615 households, and 492 families residing in the township. The population density was 51.5 PD/sqmi. There were 664 housing units at an average density of 18.7 /sqmi. The racial makeup of the township was 95.78% White, 1.26% African American, 0.33% Native American, 0.33% Asian, 0.55% from other races, and 1.75% from two or more races. Hispanic or Latino of any race were 2.52% of the population.

There were 615 households, out of which 41.6% had children under the age of 18 living with them, 66.3% were married couples living together, 8.5% had a female householder with no husband present, and 20.0% were non-families. 15.3% of all households were made up of individuals, and 5.2% had someone living alone who was 65 years of age or older. The average household size was 2.90 and the average family size was 3.17.

In the township the population was spread out, with 29.2% under the age of 18, 7.4% from 18 to 24, 30.4% from 25 to 44, 23.7% from 45 to 64, and 9.2% who were 65 years of age or older. The median age was 35 years. For every 100 females, there were 106.3 males. For every 100 females age 18 and over, there were 105.7 males.

The median income for a household in the township was $42,955, and the median income for a family was $46,830. Males had a median income of $32,632 versus $21,442 for females. The per capita income for the township was $15,833. About 3.8% of families and 8.3% of the population were below the poverty line, including 4.4% of those under age 18 and 8.6% of those age 65 or over.

title: Fairplain Township, Michigan


text:
Ferris Township, Michigan

Ferris Township is a civil township of Montcalm County in the U.S. state of Michigan. The population was 1,331 at the 2020 census.

The township was established in 1857.

Geography
Ferris Township is in eastern Montcalm County, with its eastern border following the Gratiot County line. The center of the township is 11 mi southeast of Edmore and the same distance northeast of Stanton, the county seat.

According to the U.S. Census Bureau, the township has a total area of 36.1 sqmi, of which 0.07 sqmi, or 0.20%, are water. The eastern part of the township is drained by the Pine River, a tributary of the Chippewa River flowing east toward Lake Huron, while the western side is drained by Fish Creek, a south-flowing tributary of the Maple River, part of the Grand River watershed flowing west toward Lake Michigan.

Demographics
As of the census of 2000, there were 1,379 people, 486 households, and 394 families residing in the township. The population density was 38.2 PD/sqmi. There were 566 housing units at an average density of 15.7 /sqmi. The racial makeup of the township was 98.19% White, 0.29% African American, 0.15% Native American, 0.07% Asian, 0.07% Pacific Islander, 0.29% from other races, and 0.94% from two or more races. Hispanic or Latino of any race were 1.23% of the population.

There were 486 households, out of which 38.5% had children under the age of 18 living with them, 69.1% were married couples living together, 7.2% had a female householder with no husband present, and 18.9% were non-families. 15.0% of all households were made up of individuals, and 6.0% had someone living alone who was 65 years of age or older. The average household size was 2.84 and the average family size was 3.12.

In the township the population was spread out, with 28.4% under the age of 18, 8.8% from 18 to 24, 29.9% from 25 to 44, 21.9% from 45 to 64, and 11.0% who were 65 years of age or older. The median age was 35 years. For every 100 females, there were 100.4 males. For every 100 females age 18 and over, there were 98.2 males.

The median income for a household in the township was $35,820, and the median income for a family was $36,932. Males had a median income of $29,219 versus $20,529 for females. The per capita income for the township was $15,184. About 6.7% of families and 9.7% of the population were below the poverty line, including 15.1% of those under age 18 and 4.2% of those age 65 or over.

title: Ferris Township, Michigan


text:
Greenville, Michigan

Greenville is a city in the Lower Peninsula of the U.S. state of Michigan. With a population 8,816 at the 2020 census, it is the largest city in Montcalm County. The city is the location of the establishment of the Meijer chain of stores.

History
Greenville is named after its founder, John Green, who settled in the wilderness of the southwest part of Montcalm County in 1844. Green constructed a sawmill on the Flat River that is credited for attracting other settlers. The newly formed "Green's Village" attracted many people of Danish origin who followed another early Danish settler's positive letters home regarding the area. Because of the town's heritage, Greenville celebrates the Danish Festival every year on the third weekend of August. A post office was established on January 20, 1848, with Abel French as the first postmaster. John Green had the village platted in 1853, and it was a station on the Detroit, Grand Rapids and Western Railroad. Greenville incorporated as a village in 1867 and as a city in 1871.

Hendrik Meijer, founder of Meijer's stores, moved to Greenville after immigrating to the United States from the Netherlands. He was initially a barber, but the Great Depression and lack of a proper grocery on his side of town led him to open his own store in 1934. Meijer corporation now operates stores throughout the Midwest. Hendrik's son Fred Meijer, principal architect of the modern Meijer chain, is a native son.

Greenville is home to the Fighting Falcon, the lead plane of a wave of gliders during World War II's Operation Overlord. The Falcon was purchased with funds raised by the schoolchildren of the city, and was designated the lead aircraft in recognition of this achievement.

Since the foundation of Ranney Refrigerator Co. in 1892, the town has been known as the "Refrigerator Capital of the World". It has also been home to the Gibson, White Consolidated, Frigidaire, and until recently, the Electrolux refrigerator factory. Electrolux closed the Greenville facility in early 2006, as it was in the process of relocating the factory to Ciudad Juárez in Mexico. This move impacted 2,700 employees and their families.

The city was to become the epicenter of "green" technology with the addition of solar panel manufacturer United Solar Ovonic; however, that enterprise filed for bankruptcy. It is also home to the new manufacturing and design center of Northland Marvel, an undercounter refrigeration company that just became a part of the UK-based AgaRangemaster group.

Lafayette Street, the downtown district, was placed on the National and State Register of Historic Places in November 2008.

Geography
Greenville is in southwestern Montcalm County, bordered nearly on all sides by Eureka Township and for a short distance to the north by Montcalm Township. It is 16 mi by road southwest of Stanton, the Montcalm county seat, and 33 mi northeast of Grand Rapids.

According to the United States Census Bureau, the city has a total area of 6.65 sqmi, of which 6.34 sqmi are land and 0.31 sqmi, or 4.67%, are water. The Flat River passes through the city, flowing south to join the Grand River at Lowell. Greenville contains three navigable lakes within its city limits, Baldwin, Manoka, and Como. It also contains many unnamed ponds, a peat bog, and seasonal wet lands.

The Greenville post office, with ZIP code 48838, also serves all of Eureka Township, a large portion of Montcalm Township and a smaller area of Pine Township to the north, Fairplain Township to the east, a small area of Otisco Township in Ionia County to the south, and a large part of Oakfield Township to the west and a smaller part of Grattan Township to the southwest, both in Kent County.

Major highways

 * runs east-west through the center of Greenville as Washington Street.
 * runs north-south through Greenville as Lafayette Street, crossing M-57 in the center of town.

Climate
The climatic region is typified by large seasonal temperature differences, with warm to hot (and often humid) summers and cold (sometimes severely cold) winters. According to the Köppen Climate Classification system, Greenville has a humid continental climate, abbreviated "Dfb" on climate maps.

Swimming
Baldwin Lake Beach offers a pavilion and two acres of white sand beach on the cool shores of Baldwin Lake. The swimming area is small with no docks in water off the beach. The pavilion has vending machines and changing rooms. No lifeguard oversees swimmers.

Biking
Greenville has a well-developed trail system. The eight mile long Fred Meijer Flat River Trail connects Greenville's major parks and circumnavigates the city. Greenville is also the terminus of the 41 mile long Fred Meijer Heartland Trail. This trail connects Greenville to Alma, and various other communities in Montcalm and Gratiot counties. Mountain biking is available at both the Shearer Road and Edward's Creek mountain bike paths.

Skiing
The Tower Mountain ski area offers the county's only tow rope operated skiing/sledding area and is free to the public. Greenville also offers miles of cross country skiing trails at both the Greenville Community Center and along the snow-covered bike trails in the winter.

Boating
Canoe access to the Flat River is available at Jackson's Landing, a popular starting point for paddling through the Flat River State Game area.

Ice fishing
Greenville has a proud culture of ice shanty building and annually displays some of its most technologically advanced creations on the area's many fishing lakes.

Black Field
This historic stadium was carved into a hillside south of the Union School building and was home to Greenville High School's football team since 1933. The field was donated to the school by Dr. D. K. Black and was officially dedicated on October 15, 1936. This field has since been retired and a new stadium has been built on site at Greenville Senior High.

The Fighting Falcon Museum
This historical structure was built in 1902 and was originally the Cass St School building. The building was then used as the Board of Education before being renovated and turned into the Fighting Falcon Museum.

First Congregational Church
The multi-steepled First Congregational Church was completed on June 6, 1880. The front of the building is adorned with a twelve-foot wide rose window. This building is actually the second First Congregational Church in Greenville. The original First Congregational Church was built in 1856, bought by Saint Paul's Episcopal Church and moved down the street.

Historic Main Street
Greenville's original shopping district on Lafayette street showcases early 20th century architecture from the bluffs of the Flat River to Greenville's city hall. Among longtime local businesses is Kemp Insurance Sure which has been located on Lafayette since 1879. Currently, several buildings are undergoing facade renovation, restoring them to original construction.

The Little Mermaid
A copy of Denmark's The Little Mermaid sits along the banks of the Flat River. This little statue generated an international controversy when the City of Greenville was sued for copyright infringement by the heirs of the original sculptor, Edvard Eriksen.

The Flat River Historical Museum
Established October 10, 1972, the Flat River Historical Museum stands on the banks of the Flat River on the same site where John Green built his cabin, a dam across the flat river, and the sawmill that brought jobs and the village's first residents.

Historic Armory
The Washington Street Armory was un-commissioned after the completion of the modern armory that was built next door. In 1981 it was converted into a roller rink.

The story book castle murals were completed by a local artist, Eston King. A fire in 2006 caused extensive damage to the roof and it was demolished in 2011.

Danish festival
The third weekend in August celebrates Greenville's Danish heritage as well as its modern-day Midwestern spirit.

Farming
Greenville's farms are located in Montcalm County's Soil Preservation District. Greenville is surrounded by potato, corn, dairy, and Christmas tree farms. Greenville was home to Ore-ida's tater tots division, until Oreida consolidated its operation in 1986 and Greenville's farmers were forced to diversify their crops.

Greenville has an active 4H program and each summer hosts the Montcalm County 4H Fair. This fair displays livestock competitions, tractors pulls, a busy midway, and a demolition derby.

Arts
Greenville is home to an active arts scene. The Greenville Area Recreation and Community Center is home to the Hans Christian Andersen Theater (HCAT), which puts on productions for children, teens, and adults. The Flat River Community Players also stages productions of American plays at the Greenville Community Center Theater. The award-winning Greenville High School music program consists of a marching band, concert band, jazz band, orchestra, symphonic orchestra, and the Village Green singers.

Local media
The area is served by the daily newspaper, The Daily News, headquartered in Greenville. The Daily News has a circulation around 4,500. The city has one radio station, WGLM, simulcast on FM and AM as "M106-3" and "M-1380".

Demographics
As of 2000 the median income for a household in the city was $30,453, and the median income for a family was $35,050. Males had a median income of $32,500 versus $23,338 for females. The per capita income for the city was $15,933. About 9.4% of families and 15.2% of the population were below the poverty line, including 24.1% of those under age 18 and 6.6% of those age 65 or over.

2010 census
As of the census of 2010, there were 8,481 people, 3,464 households, and 2,138 families residing in the city. The population density was 1337.7 PD/sqmi. There were 3,826 housing units at an average density of 603.5 /sqmi. The racial makeup of the city was 94.3% White, 0.3% African American, 0.5% Native American, 0.7% Asian, 0.1% Pacific Islander, 1.8% from other races, and 2.4% from two or more races. Hispanic or Latino of any race were 4.9% of the population.

There were 3,464 households, of which 35.2% had children under the age of 18 living with them, 38.8% were married couples living together, 17.1% had a female householder with no husband present, 5.8% had a male householder with no wife present, and 38.3% were non-families. 32.0% of all households were made up of individuals, and 13.8% had someone living alone who was 65 years of age or older. The average household size was 2.39 and the average family size was 2.98.

The median age in the city was 34.7 years. 26.6% of residents were under the age of 18; 9.4% were between the ages of 18 and 24; 26.3% were from 25 to 44; 22.4% were from 45 to 64; and 15.2% were 65 years of age or older. The gender makeup of the city was 47.2% male and 52.8% female.

Notable residents

 * Frederick C. Bock, bomber pilot
 * Frederik Meijer, businessman
 * Mike Vining, sergeant major
 * Ivy Winters, drag queen
 * Justin Zimmer, football player
 * Ty Hallock, football player

title: Greenville, Michigan


text:
Howard City, Michigan

Howard City is a village in Montcalm County in the U.S. state of Michigan. The population was 1,835 at the 2020 census. The village is within Reynolds Township.

History
Benjamin Ensley owned the land on which he, E. W. Muenscher, and Mr. Shaw began the settlement that Muenscher platted in 1868. It was named for William A. Howard, a Detroit railroad attorney. The Detroit, Grand Rapids and Western Railroad depot opened in 1869. A post office was established on January 12, 1870, with John B. Spencer as the first postmaster. It incorporated as a village in 1873. The post office name was shortened to "Howard" on February 2, 1895, but restored to Howard City on January 19, 1899.

The village's Main Street was initially constructed on Ensley Street, which was named after early settler Benjamin Ensley. In 1883, however, many of the wooden buildings on Ensley Street burned down. Main Street was then shifted over to Edgerton Street, its present location. The Hudson Knife factory and the Skinner and Steenman sideboard factory were two of the earliest businesses. Later, Hudson Knife Co. went through changes and became the Joslin and eventually Olsen Knife Company, which had the somewhat famous jingle, "Fatty Fatty run for your life, here comes Skinny with an Olsen Knife." Howard City schools were combined with Sand Lake schools to the south in 1962, and renamed Tri County, because students from Kent, Montcalm, and Newaygo counties all attended. The school still runs under the same moniker.

Geography
Howard City is in northwestern Montcalm County, in the southeast corner of Reynolds Township. A small portion of the village extends south into Pierson Township. The U.S. 131 freeway passes 2 mi west of the village, with access from Exit 118. U.S. 131 leads south-southwest 34 mi to Grand Rapids and north 63 mi to Cadillac. Greenville, the largest city in Montcalm County, is 25 mi southeast of Howard City.

According to the U.S. Census Bureau, the village has a total area of 2.44 sqmi, of which 0.03 sqmi, or 1.39%, are water. Tamarack Creek, a west-flowing tributary of the Little Muskegon River, passes through the north side of the village.

The Howard City post office, with ZIP code 49329, also serves much of southern Reynolds Township, as well as a large part of Winfield Township to the east, a small area of Maple Valley Township to the southeast, portions of Pierson Township to the south. It also serves parts of Croton Township to the west and Ensley Township to the southwest in Newaygo County.

2010 census
As of the census of 2010, there were 1,808 people, 685 households, and 464 families residing in the village. The population density was 714.6 PD/sqmi. There were 743 housing units at an average density of 293.7 /sqmi. The racial makeup of the village was 96.3% White, 0.6% African American, 0.6% Native American, 0.2% Asian, 0.8% from other races, and 1.5% from two or more races. Hispanic or Latino of any race were 2.4% of the population.

There were 685 households, of which 39.7% had children under the age of 18 living with them, 45.1% were married couples living together, 17.4% had a female householder with no husband present, 5.3% had a male householder with no wife present, and 32.3% were non-families. 26.4% of all households were made up of individuals, and 10.9% had someone living alone who was 65 years of age or older. The average household size was 2.63 and the average family size was 3.13.

The median age in the village was 33.6 years. 29.4% of residents were under the age of 18; 9.1% were between the ages of 18 and 24; 26.9% were from 25 to 44; 21.8% were from 45 to 64; and 12.9% were 65 years of age or older. The gender makeup of the village was 46.6% male and 53.4% female.

2000 census
As of the census of 2000, there were 1,585 people, 576 households, and 410 families residing in the village. The population density was 631.5 PD/sqmi. There were 626 housing units at an average density of 249.4 /sqmi. The racial makeup of the village was 95.90% White, 0.19% African American, 0.57% Native American, 0.13% Asian, 0.95% from other races, and 2.27% from two or more races. Hispanic or Latino of any race were 2.59% of the population.

There were 576 households, out of which 38.7% had children under the age of 18 living with them, 52.4% were married couples living together, 14.1% had a female householder with no husband present, and 28.8% were non-families. 25.2% of all households were made up of individuals, and 13.9% had someone living alone who was 65 years of age or older. The average household size was 2.75 and the average family size was 3.22.

In the village, the population was spread out, with 32.3% under the age of 18, 8.9% from 18 to 24, 27.9% from 25 to 44, 17.7% from 45 to 64, and 13.2% who were 65 years of age or older. The median age was 32 years. For every 100 females, there were 84.9 males. For every 100 females age 18 and over, there were 83.4 males.

The median income for a household in the village was $34,556, and the median income for a family was $41,250. Males had a median income of $32,241 versus $22,917 for females. The per capita income for the village was $14,076. About 5.7% of families and 10.4% of the population were below the poverty line, including 13.4% of those under age 18 and 13.1% of those age 65 or over.

Transportation

 * Indian Trails provides daily intercity bus service between Grand Rapids, Michigan and Petoskey, Michigan.

Schools
Tri County Area Schools is the main school district in Howard City. Schools include Tri County High School, Tri County Middle School, MacNaughten Elementary, Sand Lake Elementary and Edgerton Upper Elementary. The School mascot is the Viking. Sports include football, basketball, softball, baseball, wrestling, sideline cheer, competitive cheer, golf, track and field, cross country, bowling, poms and soccer. In 2009, the varsity softball team took a District title, but fell short at regionals to Petosky. Neighboring schools include Newaygo, Grant, Morley-Stanwood, Lakeview and Cedar Springs.

The district was a consolidation of the Sand Lake and Howard City school boards. It came into existence on April 3, 1962, the day members of those communities voted in favor of consolidating their schools. The consolidated schools began operation in fall 1962. Prior to the consolidation, Howard City High School served the community. Impetus for consolidation occurred when the State of Michigan adopted new standards for education which required school systems to spend additional funds. A former member of the school board of Sand Lake, Charles Northup, stated, "Howard City was almost in the same predicament as us. We figured we would have a good school system coming together." Sand Lake was a community which sought consolidation due to the financial strain from meeting the new requirements.

title: Howard City, Michigan


text:
Lakeview, Michigan

Lakeview is a village in Cato Township in Montcalm County of the U.S. state of Michigan. The population was 1,024 at the 2020 census.

History
Lakeview was first settled in 1858 and platted in 1867 by Albert S. French, a settler from New York. It had been a Native American camp site. French named it for its location on the west side of Tamarack Lake. A post office was established on October 7, 1867, with Hiram S. Barton as its first postmaster. It was a station on the Chicago, Saginaw and Canada Railroad in 1879.

Geography
Lakeview is in northern Montcalm County, in the north-central part of Cato Township. It sits on the west side of Tamarack Lake, 19 mi north of Greenville. According to the U.S. Census Bureau, the village has a total area of 1.83 sqmi, of which 1.50 sqmi are land and 0.33 sqmi, or 18.2%, are water. Tamarack Lake drains to the north, outside the village limits, to Tamarack Creek, which flows west past the village toward the Little Muskegon River and ultimately to Lake Michigan.

State highway M-46 runs along the southern edge of the village, leading east 11 mi to Edmore and west 12 mi to U.S. Route 131 near Howard City. M-91 runs south from M-46 at the Lakeview border to Greenville.

The Lakeview post office, with ZIP code 48850, serves most of Cato Township as well as part of Belvidere Township to the east, Douglass Township to the southeast, Pine Township to the south, and Winfield Township to the west. It also serves a large portion of Hinton Township to the north and Millbrook Township to the northeast in Mecosta County.

2010 census
As of the census of 2010, there were 1,007 people, 438 households, and 259 families living in the village. The population density was 662.5 PD/sqmi. There were 499 housing units at an average density of 328.3 /sqmi. The racial makeup of the village was 96.3% White, 0.4% African American, 0.4% Native American, 0.6% Asian, 0.2% Pacific Islander, 0.2% from other races, and 1.9% from two or more races. Hispanic or Latino of any race were 2.6% of the population.

There were 438 households, of which 27.9% had children under the age of 18 living with them, 39.3% were married couples living together, 16.7% had a female householder with no husband present, 3.2% had a male householder with no wife present, and 40.9% were non-families. 35.4% of all households were made up of individuals, and 16.7% had someone living alone who was 65 years of age or older. The average household size was 2.23 and the average family size was 2.86.

The median age in the village was 41.3 years. 23.1% of residents were under the age of 18; 9% were between the ages of 18 and 24; 21.8% were from 25 to 44; 24.9% were from 45 to 64; and 21.5% were 65 years of age or older. The gender makeup of the village was 46.2% male and 53.8% female.

2000 census
As of the census of 2000, there were 1,112 people, 396 households, and 287 families living in the village. The population density was 707.2 PD/sqmi. There were 452 housing units at an average density of 287.4 /sqmi. The racial makeup of the village was 97.57% White, 0.09% African American, 0.45% Native American, 0.27% Asian, 0.72% from other races, and 0.90% from two or more races. Hispanic or Latino of any race were 3.06% of the population.

There were 396 households, out of which 36.1% had children under the age of 18 living with them, 53.0% were married couples living together, 15.7% had a female householder with no husband present, and 27.3% were non-families. 24.0% of all households were made up of individuals, and 15.7% had someone living alone who was 65 years of age or older. The average household size was 2.67 and the average family size was 3.08.

In the village, the population was spread out, with 29.0% under the age of 18, 8.2% from 18 to 24, 26.5% from 25 to 44, 16.2% from 45 to 64, and 20.1% who were 65 years of age or older. The median age was 36 years. For every 100 females, there were 81.4 males. For every 100 females age 18 and over, there were 79.1 males.

The median income for a household in the village was $33,611, and the median income for a family was $38,594. Males had a median income of $28,681 versus $22,955 for females. The per capita income for the village was $14,154. About 9.8% of families and 9.9% of the population were below the poverty line, including 12.8% of those under age 18 and 8.8% of those age 65 or over.

Climate
This climatic region is typified by large seasonal temperature differences, with warm to hot (and often humid) summers and cold (sometimes severely cold) winters. According to the Köppen Climate Classification system, Lakeview has a humid continental climate, abbreviated "Dfb" on climate maps.

title: Lakeview, Michigan


text:
McBride, Michigan

McBride is a village in Montcalm County in the U.S. state of Michigan. The population was 189 at the 2020 census. The village is located within Day Township. The post office for the village, with ZIP code 48852, is named "McBrides" and provides P.O. box service to the village.

History
The village is named for Alexander B. McBride, a settler from Wayne County, New York, who built a sawmill there in 1874. A railroad station was named "McBride's Mill", while the post office named "McBrides" opened on March 26, 1878, with McBride as the first postmaster. The village was platted by D. L. Jacobs in 1877. An adjacent settlement was platted with the name "Custer" by Phipps Wado on April 2, 1878, but it became a part of McBride when that village was incorporated in 1883.

Geography
McBride is in northeastern Montcalm County, 6 mi by road northeast of Stanton, the county seat, and 4 mi south of Edmore. According to the U.S. Census Bureau, the village has a total area of 0.39 sqmi, all land.

2010 census
As of the census of 2010, there were 205 people, 83 households, and 52 families residing in the village. The population density was 539.5 PD/sqmi. There were 97 housing units at an average density of 255.3 /sqmi. The racial makeup of the village was 98.0% White, 0.5% Asian, and 1.5% from two or more races. Hispanic or Latino of any race were 1.0% of the population.

There were 83 households, of which 32.5% had children under the age of 18 living with them, 49.4% were married couples living together, 9.6% had a female householder with no husband present, 3.6% had a male householder with no wife present, and 37.3% were non-families. 33.7% of all households were made up of individuals, and 14.4% had someone living alone who was 65 years of age or older. The average household size was 2.47 and the average family size was 3.02.

The median age in the village was 39.4 years. 28.8% of residents were under the age of 18; 8.4% were between the ages of 18 and 24; 23% were from 25 to 44; 24.9% were from 45 to 64; and 15.1% were 65 years of age or older. The gender makeup of the village was 50.7% male and 49.3% female.

2000 census
As of the census of 2000, there were 232 people, 86 households, and 63 families residing in the village. The population density was 642.3 PD/sqmi. There were 94 housing units at an average density of 260.3 /sqmi. The racial makeup of the village was 98.71% White, 0.43% Native American, and 0.86% from two or more races.

There were 86 households, out of which 37.2% had children under the age of 18 living with them, 58.1% were married couples living together, 11.6% had a female householder with no husband present, and 26.7% were non-families. 24.4% of all households were made up of individuals, and 11.6% had someone living alone who was 65 years of age or older. The average household size was 2.70 and the average family size was 3.11.

In the village, the population was spread out, with 25.0% under the age of 18, 9.9% from 18 to 24, 30.2% from 25 to 44, 20.7% from 45 to 64, and 14.2% who were 65 years of age or older. The median age was 34 years. For every 100 females, there were 87.1 males. For every 100 females age 18 and over, there were 83.2 males.

The median income for a household in the village was $30,568, and the median income for a family was $30,694. Males had a median income of $25,000 versus $18,214 for females. The per capita income for the village was $13,376. About 8.2% of families and 18.8% of the population were below the poverty line, including 18.3% of those under the age of eighteen and 28.0% of those 65 or over.

title: McBride, Michigan