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Yersinia

Yersinia is a genus of bacteria in the family Yersiniaceae. Yersinia species are Gram-negative, coccobacilli bacteria, a few micrometers long and fractions of a micrometer in diameter, and are facultative anaerobes. Some members of Yersinia are pathogenic in humans; in particular, Y. pestis is the causative agent of the plague. Rodents are the natural reservoirs of Yersinia; less frequently, other mammals serve as the host. Infection may occur either through blood (in the case of Y. pestis) or in an alimentary fashion, occasionally via consumption of food products (especially vegetables, milk-derived products, and meat) contaminated with infected urine or feces.

Speculations exist as to whether or not certain Yersinia can also be spread by protozoonotic mechanisms, since Yersinia species are known to be facultative intracellular parasites; studies and discussions of the possibility of amoeba-vectored (through the cyst form of the protozoan) Yersinia propagation and proliferation are now in progress.

Microbial physiology
An interesting feature peculiar to some of the Yersinia bacteria is the ability to not only survive, but also to actively proliferate at temperatures as low as 1–4 °C (e.g., on cut salads and other food products in a refrigerator). Yersinia bacteria are relatively quickly inactivated by oxidizing agents such as hydrogen peroxide and potassium permanganate solutions.

Database
The creation of YersiniaBase, a data and tools collection for the reporting and comparison of Yersinia species genome sequence data, was reported in January 2015. The provisional representation of species addressed by the resource has been indicated in the TaxBox on this page by a superscript 'yb' beside the species name. Development of YersiniaBase was funded by the University of Malaya and the Ministry of Education, Malaysia.

Pathogenesis
Y. pestis is the causative agent of plague. The disease caused by Y. enterocolitica is called yersiniosis.

Yersinia may be associated with Crohn's disease, an inflammatory autoimmune condition of the gut. Iranian people with Crohn's disease were more likely to have had earlier exposure to refrigerators at home, consistent with its unusual ability to thrive at low temperatures.

Yersinia is implicated as one of the causes of reactive arthritis worldwide.

Also, the genus is associated with pseudoappendicitis, which is an incorrect diagnosis of appendicitis due to a similar presentation.

History
Y. pestis, the first known species, was identified in 1894 by A.E.J. Yersin, a Swiss bacteriologist, and Kitasato Shibasaburō, a Japanese bacteriologist. It was formerly described as Pasteurella pestis (known trivially as the plague-bacillus) by Lehmann and Neumann in 1896. In 1944, van Loghem reclassified the species P. pestis and P. rondentium into a new genus, Yersinia. Following the introduction of the bacteriological code, it was accepted as valid in 1980.

title: Yersinia


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Chicago flood

The Chicago flood occurred on April 13, 1992, when repair work on a bridge spanning the Chicago River damaged the wall of an abandoned and disused utility tunnel beneath the river. The resulting breach flooded basements, facilities and the underground Chicago Pedway throughout the Chicago Loop with an estimated 250 e6USgal of water. The remediation lasted for weeks, and cost about $2 billion in 1992 dollars, equivalent to $ in. The legal battles lasted for several years, and disagreement over who was at fault persists to this day.

Cause
Rehabilitation work on the Kinzie Street Bridge crossing the Chicago River required new pilings. However, when the City of Chicago specified that the old pilings be extracted and replaced by the new ones, the Great Lakes Dredge and Dock Company reported back that the old pilings were too close to the bridge tender's house, preventing proper removal without risking damaging or destroying the house. The City of Chicago then gave permission to install the new pilings 3.5 ft south of the old pilings. The crew members who began work at the site did not know that beneath the river was an abandoned Chicago Tunnel Company (CTC) tunnel that had been used in the early 20th century to transport coal and goods. One of the pilings on the east bank was driven into the bottom of the river alongside the north wall of the old tunnel. The pilings did not punch through the tunnel wall, but clay soil displaced by the piling eventually breached the wall, allowing sediment and water to seep into the tunnel. After some weeks, most of the clay between the water and the breach had liquefied, which rapidly increased the rate of flooding in the tunnel. The situation became problematic because the flood doors had been removed from the old tunnels after they fell into disuse.

Discovery of the leak
A skilled telecommunications worker inspecting a cable running through the tunnel discovered the leak while it was still passing mud and forwarded a videotape to the city, which did not see anything serious and began a bid process to repair the tunnel. The CTC tunnels were never formally a public responsibility, as most of them had been dug clandestinely, many violated private property and the collapse of the operator had failed to resolve ownership and maintenance responsibilities. Meanwhile, the mud continued to push through until the river water was able to pour in unabated, creating an immediate emergency.

Effects
The water flooded into the basements of several Loop office buildings and retail stores and an underground shopping district. The Loop and financial district were evacuated, and electrical power and gas were interrupted in most of the area as a precaution. Trading at the Chicago Board of Trade Building and the Chicago Mercantile Exchange ended in mid-morning as water seeped into their basements. At its height, some buildings had 40 ft of water in their lower levels. However, at the street level there was no water to be seen, as it was all underground.

At first, the source of the water was unclear. WMAQ radio reporter Larry Langford reported that city crews were in the process of shutting down large water mains to see if the water flow could be stopped. Monitoring police scanners, Langford heard security crews from Chicago's Merchandise Mart (near the Kinzie Street Bridge) report that the water in their basement had fish. Langford drove to the Merchandise Mart, then reported over the air that water was swirling near a piling in a manner similar to water going down a bathtub drain. Within minutes emergency services were converging on the bridge.

Repair and cleanup
Workers attempted to plug the hole, by then about 20 ft wide, with 65 truckloads of rocks, cement and old mattresses. In an attempt to slow the leak, the level of the Chicago River was lowered by opening the locks downstream of Chicago, and the freight tunnels were drained into the Chicago Deep Tunnel system. The leak was eventually stopped by placing a specialized concrete mixture supplied by Material Service Corporation (MSC) and placed by Kenny Construction. The concrete was designed by Brian Rice of MSC and was to set up so quickly that the concrete delivery trucks were provided police escorts. The concrete was placed into drilled shafts into the flooded tunnel near Kinzie Street and formed emergency plugs.

Aftermath
It took three days before the flood was cleaned up enough to allow business to begin to resume and cost the city an estimated $1.95 billion (equivalent to $ in ). Some buildings remained closed for a few weeks. Parking was banned downtown during the cleanup and some subway routes were temporarily closed or rerouted. Since it occurred near Tax Day, the IRS granted natural disaster extensions to those affected.

Eventually, the city assumed maintenance responsibility for the tunnels, and watertight hatches were installed at the river crossings. Great Lakes Dredge and Dock Co. sued the City of Chicago arguing that the city had failed to tell it about the existence of the tunnels. Insurance battles lasted for years, the central point being the definition of the accident, i.e., whether it was a "flood" or a "leak". Leaks were covered by insurance, while floods were not. Eventually it was classified as a leak, which is why many residents still call it the "Great Chicago Leak".

Today, there remains contention as to whether the mistake was the fault of the workers on-site, their parent company, or even the claim that maps provided by the City of Chicago failed to accurately depict the old tunnel systems. In fact, the Kinzie Street river crossing was clearly delineated on the city maps: the typical tunnel ran down the center of the old streets. At Kinzie Street, like some of the other river crossings, it veered off to the side as the historic Kinzie bridge (at the time of the tunnel construction) was a pivoting bridge with a central pivot in the middle of the street. Thus the original tunnels were moved to the side, as were several other bridges across the Chicago River—shown in detail on the city maps.

Court cases
In the lawsuits that followed, Great Lakes Dredge and Dock Co. was initially found liable but was later cleared after it was revealed that the city was aware the tunnel was leaking before the flood and the city had also not properly maintained the tunnel.

In addition the case went to the United States Supreme Court in which ruled that since the work was being done by a vessel in navigable waters of the Chicago River, admiralty law applied and Great Lakes's liability was greatly limited.

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

title: Chicago flood


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Salmonella

Salmonella is a genus of rod-shaped (bacillus) gram-negative bacteria of the family Enterobacteriaceae. The two known species of Salmonella are Salmonella enterica and Salmonella bongori. S. enterica is the type species and is further divided into six subspecies that include over 2,650 serotypes. Salmonella was named after Daniel Elmer Salmon (1850–1914), an American veterinary surgeon.

Salmonella species are non-spore-forming, predominantly motile enterobacteria with cell diameters between about 0.7 and 1.5 μm, lengths from 2 to 5 μm, and peritrichous flagella (all around the cell body, allowing them to move). They are chemotrophs, obtaining their energy from oxidation and reduction reactions, using organic sources. They are also facultative anaerobes, capable of generating adenosine triphosphate with oxygen ("aerobically") when it is available, or using other electron acceptors or fermentation ("anaerobically") when oxygen is not available.

Salmonella species are intracellular pathogens, of which certain serotypes cause illness such as salmonellosis. Most infections are due to the ingestion of food contaminated by feces. Typhoidal Salmonella serotypes can only be transferred between humans and can cause foodborne illness as well as typhoid and paratyphoid fever. Typhoid fever is caused by typhoidal Salmonella invading the bloodstream, as well as spreading throughout the body, invading organs, and secreting endotoxins (the septic form). This can lead to life-threatening hypovolemic shock and septic shock, and requires intensive care including antibiotics.

Nontyphoidal Salmonella serotypes are zoonotic and can be transferred from animals and between humans. They usually invade only the gastrointestinal tract and cause salmonellosis, the symptoms of which can be resolved without antibiotics. However, in sub-Saharan Africa, nontyphoidal Salmonella can be invasive and cause paratyphoid fever, which requires immediate antibiotic treatment.

Taxonomy
The genus Salmonella is part of the family of Enterobacteriaceae. Its taxonomy has been revised and has the potential to confuse. The genus comprises two species, S. bongori and S. enterica, the latter of which is divided into six subspecies: S. e. enterica, S. e. salamae, S. e. arizonae, S. e. diarizonae, S. e. houtenae, and S. e. indica. The taxonomic group contains more than 2500 serotypes (also serovars) defined on the basis of the somatic O (lipopolysaccharide) and flagellar H antigens (the Kauffman–White classification). The full name of a serotype is given as, for example, Salmonella enterica subsp. enterica serotype Typhimurium, but can be abbreviated to Salmonella Typhimurium. Further differentiation of strains to assist clinical and epidemiological investigation may be achieved by antibiotic sensitivity testing and by other molecular biology techniques such as pulsed-field gel electrophoresis, multilocus sequence typing, and, increasingly, whole genome sequencing. Historically, salmonellae have been clinically categorized as invasive (typhoidal) or noninvasive (nontyphoidal salmonellae) based on host preference and disease manifestations in humans.

History
Salmonella was first visualized in 1880 by Karl Eberth in the Peyer's patches and spleens of typhoid patients. Four years later, Georg Theodor Gaffky was able to grow the pathogen in pure culture. A year after that, medical research scientist Theobald Smith discovered what would be later known as Salmonella enterica (var. Choleraesuis). At the time, Smith was working as a research laboratory assistant in the Veterinary Division of the United States Department of Agriculture. The division was under the administration of Daniel Elmer Salmon, a veterinary pathologist. Initially, Salmonella Choleraesuis was thought to be the causative agent of hog cholera, so Salmon and Smith named it "Hog-cholera bacillus". The name Salmonella was not used until 1900, when Joseph Leon Lignières proposed that the pathogen discovered by Salmon's group be called Salmonella in his honor.

In the late 1930s, Australian bacteriologist Nancy Atkinson established a salmonella typing laboratory – one of only three in the world at the time – at the Government of South Australia's Laboratory of Pathology and Bacteriology in Adelaide (later the Institute of Medical and Veterinary Science). It was here that Atkinson described multiple new strains of salmonella, including Salmonella Adelaide, which was isolated in 1943. Atkinson published her work on salmonellas in 1957.

Serotyping
Serotyping is done by mixing cells with antibodies for a particular antigen. It can give some idea about risk. A 2014 study showed that S. Reading is very common among young turkey samples, but it is not a significant contributor to human salmonellosis. Serotyping can assist in identifying the source of contamination by matching serotypes in people with serotypes in the suspected source of infection. Appropriate prophylactic treatment can be identified from the known antibiotic resistance of the serotype.

Newer methods of "serotyping" include xMAP and real-time PCR, two methods based on DNA sequences instead of antibody reactions. These methods can be potentially faster, thanks to advances in sequencing technology. These "molecular serotyping" systems actually perform genotyping of the genes that determine surface antigens.

Detection, culture, and growth conditions
Most subspecies of Salmonella produce hydrogen sulfide, which can readily be detected by growing them on media containing ferrous sulfate, such as is used in the triple sugar iron test. Most isolates exist in two phases, a motile phase and a non-motile phase. Cultures that are nonmotile upon primary culture may be switched to the motile phase using a Craigie tube or ditch plate. RVS broth can be used to enrich for Salmonella species for detection in a clinical sample.

Salmonella can also be detected and subtyped using multiplex or real-time polymerase chain reaction (qPCR) from extracted Salmonella DNA.

Mathematical models of Salmonella growth kinetics have been developed for chicken, pork, tomatoes, and melons. Salmonella reproduce asexually with a cell division interval of 40 minutes.

Salmonella species lead predominantly host-associated lifestyles, but the bacteria were found to be able to persist in a bathroom setting for weeks following contamination, and are frequently isolated from water sources, which act as bacterial reservoirs and may help to facilitate transmission between hosts. Salmonella is notorious for its ability to survive desiccation and can persist for years in dry environments and foods.

The bacteria are not destroyed by freezing, but UV light and heat accelerate their destruction. They perish after being heated to 55 °C for 90 min, or to 60 °C for 12 min, although if inoculated in high fat, high liquid substances like peanut butter, they gain heat resistance and can survive up to 90 °C for 30 min. To protect against Salmonella infection, heating food to an internal temperature of 75 °C is recommended.

Salmonella species can be found in the digestive tracts of humans and animals, especially reptiles. Salmonella on the skin of reptiles or amphibians can be passed to people who handle the animals. Food and water can also be contaminated with the bacteria if they come in contact with the feces of infected people or animals.

Nomenclature
Initially, each Salmonella "species" was named according to clinical consideration, for example Salmonella typhi-murium (mouse-typhoid), S. cholerae-suis (pig-cholera). After host specificity was recognized not to exist for many species, new strains received species names according to the location at which the new strain was isolated.

In 1987, Le Minor and Popoff used molecular findings to argue that Salmonella consisted of only one species, S. enterica, turning former "species" names into serotypes. In 1989, Reeves et al. proposed that the serotype V should remain its own species, resurrecting the name S. bongori. The current (by 2005) nomenclature has thus taken shape, with six recognised subspecies under S. enterica: enterica (serotype I), salamae (serotype II), arizonae (IIIa), diarizonae (IIIb), houtenae (IV), and indica (VI). As specialists in infectious disease are not familiar with the new nomenclature, the traditional nomenclature remains common.

The serotype or serovar is a classification of Salmonella based on antigens that the organism presents. The Kauffman–White classification scheme differentiates serological varieties from each other. Serotypes are usually put into subspecies groups after the genus and species, with the serotypes/serovars capitalized, but not italicized: An example is Salmonella enterica serovar Typhimurium. More modern approaches for typing and subtyping Salmonella include DNA-based methods such as pulsed field gel electrophoresis, multiple-loci VNTR analysis, multilocus sequence typing, and multiplex-PCR-based methods.

In 2005, a third species, Salmonella subterranea, was proposed, but according to the World Health Organization, the bacterium reported does not belong in the genus Salmonella. In 2016, S. subterranea was proposed to be assigned to Atlantibacter subterranea, but LPSN rejects it as an invalid publication, as it was made outside of IJSB and IJSEM. GTDB and NCBI agree with the 2016 reassignment.

GTDB RS202 reports that S. arizonae, S. diarizonae, and S. houtenae should be species of their own.

Pathogenicity
Salmonella species are facultative intracellular pathogens. Salmonella can invade different cell types, including epithelial cells, M cells, macrophages, and dendritic cells. As facultative anaerobic organism, Salmonella uses oxygen to make adenosine triphosphate (ATP) in aerobic environment (i.e., when oxygen is available). However, in anaerobic environment (i.e., when oxygen is not available) Salmonella produces ATP by fermentation; by substituting one or more of four less efficient electron acceptors than oxygen at the end of the electron transport chain: sulfate, nitrate, sulfur, or fumarate.

Most infections are due to ingestion of food contaminated by animal feces, or by human feces, such as by a food-service worker at a commercial eatery. Salmonella serotypes can be divided into two main groups—typhoidal and nontyphoidal. Typhoidal serotypes include Salmonella Typhi and Salmonella Paratyphi A, which are adapted to humans and do not occur in other animals. Nontyphoidal serotypes are more common, and usually cause self-limiting gastrointestinal disease. They can infect a range of animals, and are zoonotic, meaning they can be transferred between humans and other animals.

Salmonella pathogenicity and host interaction has been studied extensively since the 2010s. Most of the important virulent genes of Salmonella are encoded in five pathogenicity islands, the so-called Salmonella pathogenicity islands (SPIs). These are chromosomal encoded and have significant contribution to bacterial-host interaction. More traits like plasmids, flagella or biofilm-related proteins can contribute in the infection. SPIs are characterised to be regulated by complex and fine-tuned regulatory networks that allow the gene expression only in the presence of the right environmental stresses.

Molecular modeling and active site analysis of SdiA homolog, a putative quorum sensor for Salmonella typhimurium pathogenicity reveals specific binding patterns of AHL transcriptional regulators. It is also known that Salmonella plasmid virulence gene spvB enhances bacterial virulence by inhibiting autophagy.

Typhoidal Salmonella
Typhoid fever is caused by Salmonella serotypes which are strictly adapted to humans or higher primates—these include Salmonella Typhi, Paratyphi A, Paratyphi B, and Paratyphi C. In the systemic form of the disease, salmonellae pass through the lymphatic system of the intestine into the blood of the patients (typhoid form) and are carried to various organs (liver, spleen, kidneys) to form secondary foci (septic form). Endotoxins first act on the vascular and nervous apparatus, resulting in increased permeability and decreased tone of the vessels, upset of thermal regulation, and vomiting and diarrhoea. In severe forms of the disease, enough liquid and electrolytes are lost to upset the water-salt metabolism, decrease the circulating blood volume and arterial pressure, and cause hypovolemic shock. Septic shock may also develop. Shock of mixed character (with signs of both hypovolemic and septic shock) is more common in severe salmonellosis. Oliguria and azotemia may develop in severe cases as a result of renal involvement due to hypoxia and toxemia.

Non-invasive
Infection with nontyphoidal serotypes of Salmonella generally results in food poisoning. Infection usually occurs when a person ingests foods that contain a high concentration of the bacteria. Infants and young children are much more susceptible to infection, easily achieved by ingesting a small number of bacteria. In infants, infection through inhalation of bacteria-laden dust is possible.

The organisms enter through the digestive tract and must be ingested in large numbers to cause disease in healthy adults. An infection can only begin after living salmonellae (not merely Salmonella-produced toxins) reach the gastrointestinal tract. Some of the microorganisms are killed in the stomach, while the surviving ones enter the small intestine and multiply in tissues. Gastric acidity is responsible for the destruction of the majority of ingested bacteria, but Salmonella has evolved a degree of tolerance to acidic environments that allows a subset of ingested bacteria to survive. Bacterial colonies may also become trapped in mucus produced in the esophagus. By the end of the incubation period, the nearby host cells are poisoned by endotoxins released from the dead salmonellae. The local response to the endotoxins is enteritis and gastrointestinal disorder.

About 2,000 serotypes of nontyphoidal Salmonella are known, which may be responsible for as many as 1.4 million illnesses in the United States each year. People who are at risk for severe illness include infants, elderly, organ-transplant recipients, and the immunocompromised.

Invasive
While in developed countries, nontyphoidal serotypes present mostly as gastrointestinal disease, in sub-Saharan Africa, these serotypes can create a major problem in bloodstream infections, and are the most commonly isolated bacteria from the blood of those presenting with fever. Bloodstream infections caused by nontyphoidal salmonellae in Africa were reported in 2012 to have a case fatality rate of 20–25%. Most cases of invasive nontyphoidal Salmonella infection (iNTS) are caused by Salmonella enterica Typhimurium or Salmonella enterica Enteritidis. A new form of Salmonella Typhimurium (ST313) emerged in the southeast of the African continent 75 years ago, followed by a second wave which came out of central Africa 18 years later. This second wave of iNTS possibly originated in the Congo Basin, and early in the event picked up a gene that made it resistant to the antibiotic chloramphenicol. This created the need to use expensive antimicrobial drugs in areas of Africa that were very poor, making treatment difficult. The increased prevalence of iNTS in sub-Saharan Africa compared to other regions is thought to be due to the large proportion of the African population with some degree of immune suppression or impairment due to the burden of HIV, malaria, and malnutrition, especially in children. The genetic makeup of iNTS is evolving into a more typhoid-like bacterium, able to efficiently spread around the human body. Symptoms are reported to be diverse, including fever, hepatosplenomegaly, and respiratory symptoms, often with an absence of gastrointestinal symptoms.

Epidemiology
Due to being considered sporadic, between 60% and 80% of salmonella infections cases go undiagnosed. In March 2010, data analysis was completed to estimate an incidence rate of 1140 per 100,000 person-years. In the same analysis, 93.8 million cases of gastroenteritis were due to salmonella infections. At the 5th percentile the estimated amount was 61.8 million cases and at the 95th percentile the estimated amount was 131.6 million cases. The estimated number of deaths due to salmonella was approximately 155,000 deaths. In 2014, in countries such as Bulgaria and Portugal, children under 4 were 32 and 82 times more likely, respectively, to have a salmonella infection. Those who are most susceptible to infection are: children, pregnant women, elderly people, and those with deficient immune systems.

Risk factors for Salmonella infections include a variety of foods. Meats such as chicken and pork have the possibility to be contaminated. A variety of vegetables and sprouts may also have salmonella. Lastly, a variety of processed foods such as chicken nuggets and pot pies may also contain this bacteria.

Successful forms of prevention come from existing entities such as the FDA, United States Department of Agriculture, and the Food Safety and Inspection Service. All of these organizations create standards and inspections to ensure public safety in the U.S. For example, the FSIS agency working with the USDA has a Salmonella Action Plan in place. Recently, it received a two-year plan update in February 2016. Their accomplishments and strategies to reduce Salmonella infection are presented in the plans. The Centers for Disease Control and Prevention also provides valuable information on preventative care, such has how to safely handle raw foods, and the correct way to store these products. In the European Union, the European Food Safety Authority created preventative measures through risk management and risk assessment. From 2005 to 2009, the EFSA placed an approach to reduce exposure to Salmonella. Their approach included risk assessment and risk management of poultry, which resulted in a reduction of infection cases by one half. In Latin America an orally administered vaccine for Salmonella in poultry developed by Dr. Sherry Layton has been introduced which prevents the bacteria from contaminating the birds.

A recent Salmonella Typhimurium outbreak has been linked to chocolate.

Global monitoring
In Germany, food-borne infections must be reported. From 1990 to 2016, the number of officially recorded cases decreased from about 200,000 to about 13,000 cases. In the United States, about 1,200,000 cases of Salmonella infection are estimated to occur each year. A World Health Organization study estimated that 21,650,974 cases of typhoid fever occurred in 2000, 216,510 of which resulted in death, along with 5,412,744 cases of paratyphoid fever.

Molecular mechanisms of infection
The mechanisms of infection differ between typhoidal and nontyphoidal serotypes, owing to their different targets in the body and the different symptoms that they cause. Both groups must enter by crossing the barrier created by the intestinal cell wall, but once they have passed this barrier, they use different strategies to cause infection.

Switch to virulence
While travelling to their target tissue in the gastrointestinal tract, Salmonella is exposed to stomach acid, to the detergent-like activity of bile in the intestine, to decreasing oxygen supply, to the competing normal gut flora, and finally to antimicrobial peptides present on the surface of the cells lining the intestinal wall. All of these form stresses that Salmonella can sense and reacts against, and they form virulence factors and as such regulate the switch from their normal growth in the intestine into virulence.

The switch to virulence gives access to a replication niche inside the host (such as humans), and can be summarised into several stages:

 * 1) Approach, in which they travel towards a host cell via intestinal peristalsis and through active swimming via the flagella, penetrate the mucus barrier, and locate themselves close to the epithelium lining the intestine,
 * 2) Adhesion, in which they adhere to a host cell using bacterial adhesins and a type III secretion system,
 * 3) Invasion, in which Salmonella enter the host cell (see variant mechanisms below),
 * 4) Replication, in which the bacterium may reproduce inside the host cell,
 * 5) Spread, in which the bacterium can spread to other organs via cells in the blood (if it succeeded in avoiding the immune defence). Alternatively, bacteria can go back towards the intestine, re-seeding the intestinal population.
 * 6) Re-invasion (a secondary infection, if now at a systemic site) and further replication.

Mechanisms of entry
Nontyphoidal serotypes preferentially enter M cells on the intestinal wall by bacterial-mediated endocytosis, a process associated with intestinal inflammation and diarrhoea. They are also able to disrupt tight junctions between the cells of the intestinal wall, impairing the cells' ability to stop the flow of ions, water, and immune cells into and out of the intestine. The combination of the inflammation caused by bacterial-mediated endocytosis and the disruption of tight junctions is thought to contribute significantly to the induction of diarrhoea.

Salmonellae are also able to breach the intestinal barrier via phagocytosis and trafficking by CD18-positive immune cells, which may be a mechanism key to typhoidal Salmonella infection. This is thought to be a more stealthy way of passing the intestinal barrier, and may, therefore, contribute to the fact that lower numbers of typhoidal Salmonella are required for infection than nontyphoidal Salmonella. Salmonella cells are able to enter macrophages via macropinocytosis. Typhoidal serotypes can use this to achieve dissemination throughout the body via the mononuclear phagocyte system, a network of connective tissue that contains immune cells, and surrounds tissue associated with the immune system throughout the body.

Much of the success of Salmonella in causing infection is attributed to two type III secretion systems (T3SS) which are expressed at different times during the infection. The T3SS-1 enables the injection of bacterial effectors within the host cytosol. These T3SS-1 effectors stimulate the formation of membrane ruffles allowing the uptake of Salmonella by nonphagocytic cells. Salmonella further resides within a membrane-bound compartment called the Salmonella-Containing Vacuole (SCV). The acidification of the SCV leads to the expression of the T3SS-2. The secretion of T3SS-2 effectors by Salmonella is required for its efficient survival in the host cytosol and establishment of systemic disease. In addition, both T3SS are involved in the colonization of the intestine, induction of intestinal inflammatory responses and diarrhea. These systems contain many genes which must work cooperatively to achieve infection.

The AvrA toxin injected by the SPI1 type III secretion system of S. Typhimurium works to inhibit the innate immune system by virtue of its serine/threonine acetyltransferase activity, and requires binding to eukaryotic target cell phytic acid (IP6). This leaves the host more susceptible to infection.

Clinical symptoms
Salmonellosis is known to be able to cause back pain or spondylosis. It can manifest as five clinical patterns: gastrointestinal tract infection, enteric fever, bacteremia, local infection, and the chronic reservoir state. The initial symptoms are nonspecific fever, weakness, and myalgia among others. In the bacteremia state, it can spread to any parts of the body and this induces localized infection or it forms abscesses. The forms of localized Salmonella infections are arthritis, urinary tract infection, infection of the central nervous system, bone infection, soft tissue infection, etc. Infection may remain as the latent form for a long time, and when the function of reticular endothelial cells is deteriorated, it may become activated and consequently, it may secondarily induce spreading infection in the bone several months or several years after acute salmonellosis.

A 2018 Imperial College London study also shows how salmonella disrupt specific arms of the immune system (e.g. 3 of 5 NF-kappaB proteins) using a family of zinc metalloproteinase effectors, leaving others untouched. Salmonella thyroid abscess has also been reported.

Resistance to oxidative burst
A hallmark of Salmonella pathogenesis is the ability of the bacterium to survive and proliferate within phagocytes. Phagocytes produce DNA-damaging agents such as nitric oxide and oxygen radicals as a defense against pathogens. Thus, Salmonella species must face attack by molecules that challenge genome integrity. Buchmeier et al. showed that mutants of S. enterica lacking RecA or RecBC protein function are highly sensitive to oxidative compounds synthesized by macrophages, and furthermore these findings indicate that successful systemic infection by S. enterica requires RecA- and RecBC-mediated recombinational repair of DNA damage.

Host adaptation
S. enterica, through some of its serotypes such as Typhimurium and Enteritidis, shows signs of the ability to infect several different mammalian host species, while other serotypes such as Typhi seem to be restricted to only a few hosts. Some of the ways that Salmonella serotypes have adapted to their hosts include loss of genetic material and mutation. In more complex mammalian species, immune systems, which include pathogen specific immune responses, target serovars of Salmonella through binding of antibodies to structures such as flagella. Through the loss of the genetic material that codes for a flagellum to form, Salmonella can evade a host's immune system. mgtC leader RNA from bacteria virulence gene (mgtCBR operon) decreases flagellin production during infection by directly base pairing with mRNAs of the fljB gene encoding flagellin and promotes degradation. In the study by Kisela et al., more pathogenic serovars of S. enterica were found to have certain adhesins in common that have developed out of convergent evolution. This means that, as these strains of Salmonella have been exposed to similar conditions such as immune systems, similar structures evolved separately to negate these similar, more advanced defenses in hosts. Still, many questions remain about the way that Salmonella has evolved into so many different types, but Salmonella may have evolved through several phases. As Baumler et al. have suggested, Salmonella most likely evolved through horizontal gene transfer, formation of new serovars due to additional pathogenicity islands and through an approximation of its ancestry. So, Salmonella could have evolved into its many different serotypes through gaining genetic information from different pathogenic bacteria. The presence of several pathogenicity islands in the genome of different serotypes has lent credence to this theory.

Salmonella sv. Newport has signs of adaptation to a plant colonization lifestyle, which may play a role in its disproportionate association with foodborne illness linked to produce. A variety of functions selected for during sv. Newport persistence in tomatoes have been reported to be similar to those selected for in sv. Typhimurium from animal hosts. The papA gene, which is unique to sv. Newport, contributes to the strain's fitness in tomatoes, and has homologs in genomes of other Enterobacteriaceae that are able to colonize plant and animal hosts.

Research
In addition to their importance as pathogens, nontyphoidal Salmonella species such as S. enterica serovar Typhimurium are commonly used as homologues of typhoid species. Many findings are transferable and it attenuates the danger for the researcher in case of contamination, but is also limited. For example, it is not possible to study specific typhoidal toxins using this model. However, strong research tools such as the commonly-used mouse intestine gastroenteritis model build upon the use of Salmonella Typhimurium.

For genetics, S. Typhimurium has been instrumental in the development of genetic tools that led to an understanding of fundamental bacterial physiology. These developments were enabled by the discovery of the first generalized transducing phage P22 in S. Typhimurium, that allowed quick and easy genetic editing. In turn, this made fine structure genetic analysis possible. The large number of mutants led to a revision of genetic nomenclature for bacteria. Many of the uses of transposons as genetic tools, including transposon delivery, mutagenesis, and construction of chromosome rearrangements, were also developed in S. Typhimurium. These genetic tools also led to a simple test for carcinogens, the Ames test.

As a natural alternative to traditional antimicrobials, phages are being recognised as highly effective control agents for Salmonella and other foodborne bacteria.

Ancient DNA
S. enterica genomes have been reconstructed from up to 6,500 year old human remains across Western Eurasia, which provides evidence for geographic widespread infections with systemic S. enterica during prehistory, and a possible role of the Neolithization process in the evolution of host adaptation. Additional reconstructed genomes from colonial Mexico suggest S. enterica as the cause of cocoliztli, an epidemic in 16th-century New Spain.

title: Salmonella


text:
Paul Reuter

Paul Julius Reuter (born Israel Beer Josaphat; 21 July 1816 – 25 February 1899), later ennobled as Freiherr von Reuter (Baron von Reuter), was a German-born British entrepreneur who was a pioneer of telegraphy and news reporting. He was a reporter, media owner, and the founder of the Reuters news agency, which became part of the Thomson Reuters conglomerate in 2008.

Life and career
Reuter was born as Israel Beer Josaphat in Kassel, Electorate of Hesse (now part of the Federal Republic of Germany). His father, Samuel Levi Josaphat, was a rabbi. His mother was Betty Sanders. In Göttingen, Reuter met Carl Friedrich Gauss, who was experimenting with the transmission of electrical signals via wire.

On 16 November 1845, he converted to Christianity in a ceremony at St. George's German Lutheran Chapel in London, and changed his name to Paul Julius Reuter. One week later, in the same chapel, he married Ida Maria Elizabeth Clementine Magnus of Berlin, daughter of a German banker.

A former bank clerk, in 1847 he became a partner in Reuter and Stargardt, a Berlin book-publishing firm. The distribution of radical pamphlets by the firm at the beginning of the 1848 Revolution may have focused official scrutiny on Reuter. Later that year, he left for Paris and worked in Charles-Louis Havas' news agency, Agence Havas, the future Agence France Presse.

As telegraphy evolved, Reuter founded his own news agency in Aachen, transferring messages between Brussels and Aachen using homing pigeons and thus linking Berlin and Paris. Speedier than the post train, pigeons gave Reuter faster access to financial news from the Paris stock exchange. Eventually, pigeons were replaced by a direct telegraph link.

A telegraph line was under construction between Britain and continental Europe, so Reuter moved to London, renting an office near the Stock Exchange. In 1863, he privately erected a telegraph link to Crookhaven, the farthest south-western point of Ireland. On nearing Crookhaven, ships from the U.S. threw canisters containing news into the sea. These were retrieved by Reuters and telegraphed directly to London, arriving long before the ships reached Cork.

On 17 March 1857, Reuter was naturalised as a British subject. On 7 September 1871, the Duke of Saxe-Coburg and Gotha granted him the noble title of Freiherr (baron). In November 1891, Queen Victoria granted him (and his male-line successors) the right to use that German title (listed as Baron von Reuter) in Britain.

In 1872, Nasir al-Din Shah, the Shah of Iran, signed a surprisingly lopsided concession agreement with Reuter. George Curzon wrote that: [t]he concession was dated July 25, 1872. When published to the world, it was found to contain the most complete and extraordinary surrender of the entire industrial resources of a kingdom into foreign hands that has probably ever been dreamed of, much less accomplished, in history. Exclusive of the clauses referring to railroads and tramways, which conferred an absolute monopoly of both those undertakings upon Baron de Reuter for the space of seventy years, the concession also handed over to him the exclusive working for the same period of all Persian mines, except those of goldsilver, and precious stones; the monopoly of the government forests, all uncultivated land being embraced under that designation; the exclusive construction of canals, kanats, and irrigation works of every description; the first refusal of a national bank, and of all future enterprises connected with the introduction of roads, telegraphs, mills, factories, workshops, and public works of every description; and a farm of the entire customs of the empire for a period of twenty-five years from March 1, 1874, upon payment to the Shah of a stipulated sum for the first five years, and of an additional sixty per cent of the net revenue for the remaining twenty. With respect to the other profits, twenty per cent of those accruing from railways, and fifteen per cent of those derived from all other sources, were reserved for the Persian Government.

The Reuter concession was immediately denounced by all ranks of businessmen, clergy, and nationalists of Persia, and it was quickly forced into cancellation.

Marriage and children
In 1845, Reuter married Ida Maria Magnus, daughter of Friedrich Martin Magnus, a German banker in Berlin. They had three sons: Herbert, who became the 2nd baron (succeeded by his son Hubert as 3rd baron), George and Alfred. Clementine Maria, one of his daughters, married Count Otto Stenbock (diplomat), and after Stenbock's death, Sir Herbert Chermside, a governor of Queensland.

The 2nd baron's brother George had two sons, Oliver (who became the 4th baron) and Ronald. The last member of the family, Marguerite, Baroness de Reuter, widow of the 4th baron and Paul Julius Reuter's granddaughter-in-law, died on 25 January 2009, at the age of 96.

Death and legacy
Reuter died in 1899 in London, United Kingdom

Reuter was portrayed by Edward G. Robinson in the Warner Bros. biographical film A Dispatch from Reuters (1941).

The Reuters News Agency commemorated the 100th anniversary of its founder's death by launching a university award (the Paul Julius Reuter Innovation Award) in Germany.

title: Paul Reuter


text:
Server (computing)

A server is a computer that provides information to other computers called "clients" on computer network. This architecture is called the client–server model. Servers can provide various functionalities, often called "services", such as sharing data or resources among multiple clients or performing computations for a client. A single server can serve multiple clients, and a single client can use multiple servers. A client process may run on the same device or may connect over a network to a server on a different device. Typical servers are database servers, file servers, mail servers, print servers, web servers, game servers, and application servers.

Client–server systems are usually most frequently implemented by (and often identified with) the request–response model: a client sends a request to the server, which performs some action and sends a response back to the client, typically with a result or acknowledgment. Designating a computer as "server-class hardware" implies that it is specialized for running servers on it. This often implies that it is more powerful and reliable than standard personal computers, but alternatively, large computing clusters may be composed of many relatively simple, replaceable server components.

History
The use of the word server in computing comes from queueing theory, where it dates to the mid 20th century, being notably used in (along with "service"), the paper that introduced Kendall's notation. In earlier papers, such as the, more concrete terms such as "[telephone] operators" are used.

In computing, "server" dates at least to RFC 5 (1969), one of the earliest documents describing ARPANET (the predecessor of Internet), and is contrasted with "user", distinguishing two types of host: "server-host" and "user-host". The use of "serving" also dates to early documents, such as RFC 4, contrasting "serving-host" with "using-host".

The Jargon File defines server in the common sense of a process performing service for requests, usually remote, with the 1981 version reading: "SERVER n. A kind of DAEMON which performs a service for the requester, which often runs on a computer other than the one on which the server runs." The average utilization of a server in the early 2000s was 5 to 15%, but with the adoption of virtualization this figure started to increase to reduce the number of servers needed.

Operation
Strictly speaking, the term server refers to a computer program or process (running program). Through metonymy, it refers to a device used for (or a device dedicated to) running one or several server programs. On a network, such a device is called a host. In addition to server, the words serve and service (as verb and as noun respectively) are frequently used, though servicer and servant are not. The word service (noun) may refer to the abstract form of functionality, e.g. Web service. Alternatively, it may refer to a computer program that turns a computer into a server, e.g. Windows service. Originally used as "servers serve users" (and "users use servers"), in the sense of "obey", today one often says that "servers serve data", in the same sense as "give". For instance, web servers "serve [up] web pages to users" or "service their requests".

The server is part of the client–server model; in this model, a server serves data for clients. The nature of communication between a client and server is request and response. This is in contrast with peer-to-peer model in which the relationship is on-demand reciprocation. In principle, any computerized process that can be used or called by another process (particularly remotely, particularly to share a resource) is a server, and the calling process or processes is a client. Thus any general-purpose computer connected to a network can host servers. For example, if files on a device are shared by some process, that process is a file server. Similarly, web server software can run on any capable computer, and so a laptop or a personal computer can host a web server.

While request–response is the most common client-server design, there are others, such as the publish–subscribe pattern. In the publish-subscribe pattern, clients register with a pub-sub server, subscribing to specified types of messages; this initial registration may be done by request-response. Thereafter, the pub-sub server forwards matching messages to the clients without any further requests: the server pushes messages to the client, rather than the client pulling messages from the server as in request-response.

Purpose
The role of a server is to share data as well as to share resources and distribute work. A server computer can serve its own computer programs as well; depending on the scenario, this could be part of a quid pro quo transaction, or simply a technical possibility. The following table shows several scenarios in which a server is used. Almost the entire structure of the Internet is based upon a client–server model. High-level root nameservers, DNS, and routers direct the traffic on the internet. There are millions of servers connected to the Internet, running continuously throughout the world and virtually every action taken by an ordinary Internet user requires one or more interactions with one or more servers. There are exceptions that do not use dedicated servers; for example, peer-to-peer file sharing and some implementations of telephony (e.g. pre-Microsoft Skype).

Hardware

Hardware requirement for servers vary widely, depending on the server's purpose and its software. Servers often are more powerful and expensive than the clients that connect to them.

The name server is used both for the hardware and software pieces. For the hardware servers, it is usually limited to mean the high-end machines although software servers can run on a variety of hardwares.

Since servers are usually accessed over a network, many run unattended without a computer monitor or input device, audio hardware and USB interfaces. Many servers do not have a graphical user interface (GUI). They are configured and managed remotely. Remote management can be conducted via various methods including Microsoft Management Console (MMC), PowerShell, SSH and browser-based out-of-band management systems such as Dell's iDRAC or HP's iLo.

Large servers
Large traditional single servers would need to be run for long periods without interruption. Availability would have to be very high, making hardware reliability and durability extremely important. Mission-critical enterprise servers would be very fault tolerant and use specialized hardware with low failure rates in order to maximize uptime. Uninterruptible power supplies might be incorporated to guard against power failure. Servers typically include hardware redundancy such as dual power supplies, RAID disk systems, and ECC memory, along with extensive pre-boot memory testing and verification. Critical components might be hot swappable, allowing technicians to replace them on the running server without shutting it down, and to guard against overheating, servers might have more powerful fans or use water cooling. They will often be able to be configured, powered up and down, or rebooted remotely, using out-of-band management, typically based on IPMI. Server casings are usually flat and wide, and designed to be rack-mounted, either on 19-inch racks or on Open Racks.

These types of servers are often housed in dedicated data centers. These will normally have very stable power and Internet and increased security. Noise is also less of a concern, but power consumption and heat output can be a serious issue. Server rooms are equipped with air conditioning devices.

Clusters
A server farm or server cluster is a collection of computer servers maintained by an organization to supply server functionality far beyond the capability of a single device. Modern data centers are now often built of very large clusters of much simpler servers, and there is a collaborative effort, Open Compute Project around this concept.

Appliances
A class of small specialist servers called network appliances are generally at the low end of the scale, often being smaller than common desktop computers.

Mobile
A mobile server has a portable form factor, e.g. a laptop. In contrast to large data centers or rack servers, the mobile server is designed for on-the-road or ad hoc deployment into emergency, disaster or temporary environments where traditional servers are not feasible due to their power requirements, size, and deployment time. The main beneficiaries of so-called "server on the go" technology include network managers, software or database developers, training centers, military personnel, law enforcement, forensics, emergency relief groups, and service organizations. To facilitate portability, features such as the keyboard, display, battery (uninterruptible power supply, to provide power redundancy in case of failure), and mouse are all integrated into the chassis.

Operating systems
On the Internet, the dominant operating systems among servers are UNIX-like open-source distributions, such as those based on Linux and FreeBSD, with Windows Server also having a significant share. Proprietary operating systems such as z/OS and macOS Server are also deployed, but in much smaller numbers. Servers that run Linux are commonly used as Webservers or Databanks. Windows Servers are used for Networks that are made out of Windows Clients.

Specialist server-oriented operating systems have traditionally had features such as:
 * GUI not available or optional
 * Ability to reconfigure and update both hardware and software to some extent without restart
 * Advanced backup facilities to permit regular and frequent online backups of critical data,
 * Transparent data transfer between different volumes or devices
 * Flexible and advanced networking capabilities
 * Automation capabilities such as daemons in UNIX and services in Windows
 * Tight system security, with advanced user, resource, data, and memory protection.
 * Advanced detection and alerting on conditions such as overheating, processor and disk failure.

In practice, today many desktop and server operating systems share similar code bases, differing mostly in configuration.

Energy consumption
In 2010, data centers (servers, cooling, and other electrical infrastructure) were responsible for 1.1-1.5% of electrical energy consumption worldwide and 1.7-2.2% in the United States. One estimate is that total energy consumption for information and communications technology saves more than 5 times its carbon footprint in the rest of the economy by increasing efficiency.

Global energy consumption is increasing due to the increasing demand of data and bandwidth. Natural Resources Defense Council (NRDC) states that data centers used 91 billion kilowatt hours (kWh) electrical energy in 2013 which accounts to 3% of global electricity usage.

Environmental groups have placed focus on the carbon emissions of data centers as it accounts to 200 million metric tons of carbon dioxide in a year.

title: Server (computing)