SALMONELLA

Salmonella is a genus of rod-shaped, Gram-negative, non-spore-forming, predominantly motile enterobacteria with diameters around 0.7 to 1.5 µm, lengths from 2 to 5 µm, and flagella that grade in all directions (i.e., peritrichous). They are chemoorganotrophs, obtaining their energy from oxidation and reduction reactions using organic sources, and are facultative anaerobes. Most species produce hydrogen sulfide, which can readily be detected by growing them on media containing ferrous sulfate, such as TSI. Most isolates exist in two phases: a motile phase I and a nonmotile phase II. Cultures that are nonmotile upon primary culture may be switched to the motile phase using a Cragie tube. Salmonella is closely related to the Escherichia genus and are found worldwide in cold- and warm-blooded animals (including humans), and in the environment. They cause illnesses such as typhoid fever, paratyphoid fever, and foodborne illness.

SALMONELLA AS DISEASE-CAUSING AGENTS

Salmonella infections are zoonotic and can be transferred between humans and nonhuman animals. Many infections are due to ingestion of contaminated food. For example, recent FDA studies link Guatemalan cantaloupes with Salmonella Panama. In speaking of other salmonella serotypes, enteritis Salmonella and Salmonella typhoid/paratyphoid Salmonella,the latter—because of a special virulence factor and a capsule protein (virulence antigen)—can cause serious illness, such as Salmonella enterica subsp. enterica serovar Typhi. Salmonella typhi is adapted to humans and does not occur in other animals. Salmonella species are facultative intracellular pathogens that enter cells via macropinosomes

ENTERITIS SALMONELLOSIS OR FOOD POISNING

This is a group consisting of potentially every other serotype (over a thousand) of the Salmonella bacteria, most of which have never been found in humans. These are encountered in various Salmonella species, most having never been linked to a specific host, but can also infect humans. It is therefore a zoonotic disease. The organism enters through the digestive tract and must be ingested in large numbers to cause disease in healthy adults. Gastric acidity is responsible for the destruction of the majority of ingested bacteria. Salmonellosis is a disease caused by raw or undercooked food. Infection usually occurs when a person ingests foods that contain a high concentration of the bacteria, similar to a culture medium. However, infants and young children are much more susceptible to infection, easily achieved by ingesting a small number of bacteria. In infants, contamination through inhalation of bacteria-laden dust is possible. After a short incubation period of a few hours to one day, the germs multiply in the intestinal lumen, causing an intestinal inflammation with diarrhea that is often mucopurulent and bloody. In infants, dehydration can cause a state of severe toxicosis. The symptoms are usually mild. Normally, no sepsis occurs, but it can occur exceptionally as a complication in weakened or elderly patients (e.g., Hodgkin's disease). Extraintestinal localizations are possible, especially Salmonella meningitis in children, osteitis, etc. Enteritis Salmonella (e.g., Salmonella enterica subsp. enterica serovar enteritidis) can cause diarrhea, which usually does not require antibiotic treatment. However, in people at risk such as infants, small children, the elderly, Salmonella infections can become very serious, leading to complications. If these are not treated, HIV patients and those with suppressed immunity can become seriously ill. Children with sickle cell anaemia who are infected with Salmonella may develop osteomyelitis. In Germany, Salmonella infections must be reported. Between 1990 and 2005, the number of officially recorded cases decreased from approximately 200,000 to approximately 50,000 cases. Every fifth person in Germany is thought to carry Salmonella. In the USA, about 40,000 cases of Salmonella infection are reported each year. According to the World Health Organization, over 16 million people worldwide are infected with typhoid fever each year, with 500,000 to 600,000 fatal cases. Salmonella bacteria can survive for weeks outside a living body, and they are not destroyed by freezing. Ultraviolet radiation and heat accelerate their demise; they perish after being heated to 55 °C (131 °F) for 90 min, or to 60 °C (140 °F) for 12 min. To protect against Salmonella infection, heating food for at least ten minutes at 75 °C (167 °F) is recommended, so the centre of the food reaches this temperature. The AvrA toxin injected by the type three secretion system of Salmonella 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. In a 2011 paper, Yale University School of Medicine researchers described in detail how Salmonella is able to make these proteins line up in just the right sequence to invade host cells. "These mechanisms present us with novel targets that might form the basis for the development of an entirely new class of antimicrobials," said Professor Dr. Jorge Galan, senior author of the paper and the Lucille P. Markey Professor of Microbial Pathogenesis and chair of the Section of Microbial Pathogenesis at Yale. In the new National Institutes of Health-funded study, Galan and colleagues identify what they call a bacterial sorting platform, which attracts needed proteins and lines them up in a specific order. If the proteins do not line up properly, Salmonella, as well as many other bacterial pathogens, cannot "inject" them into host cells to commandeer host cell functions, the lab has found. Understanding how this machine works raises the possibility of new therapies that disable this protein delivery machine, thwarting the ability of the bacterium to become pathogenic. The process would not kill the bacteria as most antibiotics do, but would cripple its ability to do harm. In theory, this means bacteria such as Salmonella might not develop resistance to new therapies as quickly as they usually do to conventional antibiotics. Most people with salmonellosis develop diarrhea, fever, vomiting, and abdominal cramps 12 to 72 hours after infection. In most cases, the illness lasts four to seven days, and most people recover without treatment. In some cases, though, the diarrhea may be so severe, the patient becomes dangerously dehydrated and must be taken to a hospital. At the hospital, the patient may receive intravenous fluids to treat the dehydration, and may be given medications to provide symptomatic relief, such as fever reduction. In severe cases, the Salmonella infection may spread from the intestines to the blood stream, and then to other body sites, and can cause death, unless the person is treated promptly with antibiotics. The elderly, infants, and those with impaired immune systems are more likely to develop severe illness. Some people afflicted with salmonellosis later experience reactive arthritis, which can have long-lasting, disabling effects. An infectious process can only begin after living salmonellae (not only their toxins) reach the gastrointestinal tract. Some of the microorganisms are killed in the stomach, while the surviving salmonellae enter the small intestine and multiply in tissues (localized form). By the end of the incubation period, the macro-organisms are poisoned by endotoxins released from the dead salmonellae. The local response to the endotoxins is enteritis and gastrointestinal disorder. In the generalized 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, manifested by increased permeability and decreased tone of the vessels, upset thermal regulation, vomiting and diarrhea. In severe forms of the disease, enough liquid and electrolytes are lost to upset the water-salt metabolism, to decrease the circulating blood volume and arterial pressure, and to cause hypovolemic shock. Septic shock may develop. Shock of mixed character (with signs of both hypovolemic and septic shock) are more common in severe salmonellosis. Oliguria and azotemia develop in severe cases as a result of renal involvement due to hypoxia and toxemia.

HISTORY

The genus Salmonella was named after Daniel Elmer Salmon, an American veterinary pathologist. While Theobald Smith was the actual discoverer of the type bacterium (Salmonella enterica var. choleraesuis) in 1885, Dr. Salmon was the administrator of the USDA research program, and thus the organism was named after him by Smith. Smith and Salmon had been searching for the cause of common hog cholera and proposed this organism as the causal agent. Later research, however, would show this organism (now known as Salmonella enterica) rarely causes enteric symptoms in pigs, and was thus not the agent they were seeking (which was eventually shown to be a virus). However, related bacteria in the genus Salmonella were eventually shown to cause other important infectious diseases. The genus Salmonella was finally formally adopted in 1900 by J. Lignières for the many species of Salmonella, after Smith's first type-strain Salmonella cholerae suis.

SALMONELLA NOMENCLATURE

Initially, each Salmonella species was named according to clinical considerations, e.g., Salmonella typhi-murium (mouse typhoid fever), S. cholerae-suis (hog cholera). After it was recognized that host specificity did not exist for many species, new strains (or serovar, short for serological variants) received species names according to the location at which the new strain was isolated. Later, molecular findings led to the hypothesis that Salmonella consisted of only one species, S. enterica, and the serovar were classified into six groups, two of which are medically relevant. But as this now formalized nomenclature is not in harmony with the traditional usage familiar to specialists in microbiology and infectologists, the traditional nomenclature is common. Currently, there are three recognized species: S. enterica, S. bongori and S. subterranean, with six main subspecies: enterica (I), salamae (II), arizonae (IIIa), diarizonae (IIIb), houtenae (IV), and indica (VI). Historically, serotype (V) was bongori, which is now considered its own species. The serovar (i.e. serotype) is a classification of Salmonella into subspecies based on antigens that the organism presents. It is based on the Kauffman-White classification scheme that differentiates serological varieties from each other. Serotypes are usually put into subspecies groups after the genus and species, with the serovars/sertypes capitalized but not italicized: an example is Salmonella enterica serovar Typhimurium. Newer methods for Salmonella typing and subtyping include genome-based methods such as pulsed field gel electrophoresis (PFGE), Multiple Loci VNTR Analysis (MLVA), Multilocus sequence typing (MLST) and (multiplex-) PCR-based methods

GENETICS

Serovar Typhimurium has considerable diversity and may be very old. The majority of the isolates belong to a single clonal complex. Isolates are divided into phage types, but some phage types do not have a single origin as determined using mutational changes. Phage type DT104 is heterogeneous and represented in multiple sequence types, with its multidrug-resistant variant being the most successful and causing epidemics in many parts of the planet. Serovar Typhi is relatively young compared to Typhimurium, and probably originated approximately 30,000-50,000 years ago.

SOURCE OF INFECTION

Infected food, often gaining an unusual look or smell, then is introduced into the stream of commerce; Poor kitchen hygiene, especially problematic in institutional kitchens and restaurants because this can lead to a significant outbreak; Excretions from either sick or infected but apparently clinically healthy people and animals (especially endangered are caregivers and animals); Polluted surface water and standing water (such as in shower hoses or unused water dispensers); Unhygienically thawed fowl (the meltwater contains many bacteria); An association with reptiles (pet tortoises, snakes, iguanas and frogs, but primarily aquatic turtles) is well described. Salmonella bacteria can survive for some time without a host; thus, they are frequently found in polluted water, contamination from the excrement of carrier animals being particularly important.

NEW ANTIBIOTIC-RESISTANT STRAINS

Non-typhoidal salmonella (iNTS) Africa, a new form of the germ, emerged in the southeast of the continent 52 years ago, followed by a second wave, which came out of central Africa 17 years later. The second wave of iNTS began 35 years ago, possibly in the Congo Basin, and early in the event picked up a gene making it resistant to the antibiotic chloramphenicol. There is an urgency to develop an effective salmonella vaccine because of the recent outbreaks in Africa of antibiotic-resistant strains of the food-borne bacteria that is killing hundreds of thousands of people there, as well as the heavy annual worldwide death toll each year. People with HIV are greatly affected. A recently identified set of antigens (molecules in the invading bacteria that trigger an immune response) that is common to both mice and humans, provide a foundation for developing a protective salmonella vaccine that could be on the market as early as 2016. This is good news because no new, effective antibiotics are on the horizon. In sub-Saharan the variant is the cause of an enigmatic disease called invasive non-typhoidal salmonella (iNTS), which affects Africa far more than other continents. Its genetic makeup is evolving into a more typhoid-like bacteria, able to efficiently spread around the human body.

VACCINE STATUS

Researchers say they have paved the way toward an effective Salmonella vaccine by identifying eight antigenic molecules from human and mouse infections. These antigens provide the research community with a foundation for developing a protective salmonella vaccine.

DEATHS

About 142,021 (reported) Americans are infected each year with Salmonella enteritidis from chicken eggs, and about 30 die. The shell of the egg may be contaminated with Salmonella by feces or environment, or its interior (yolk) may be contaminated by penetration of the bacteria through the porous shell or from a hen whose infected ovaries contaminate the egg during egg formation. Nevertheless, such interior egg yolk contamination is theoretically unlikely. Even under natural conditions, the rate of infection was very small (0.6% in a study of naturally-contaminated eggs and 3.0% among artificially- and heavily-infected hens). In 2010, an analysis of death certificates in the United States identified a total of 1,316 Salmonella-related deaths from 1990 to 2006. These were predominantly among older adults and those who were immunocompromised.

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