In a new study, Cheryl Nickerson and her colleagues at the Biodesign Institute at Arizona State University and NASA’s Johnson Space Center have demonstrated for the first time that a distinct form of Salmonella which has emerged in sub-Saharan Africa can cause lethal infections not only in humans but in mice. The Salmonella strain used in this study, D23580, is part of a group of closely related strains collectively known as ST313. It was shown to more rapidly reach and colonize tissues of the spleen and gallbladder in mice compared to a well-characterized “classic” Salmonella strain. In results appearing in the journal PLOS Neglected Tropical Diseases, lead authors Jiseon Yang and Jennifer Barrila also established a critical variable of the pathogen known as LD50 — a measure of the median lethal dose (LD) necessary to produce a fatal infection — marking the first report of the entire natural course of disease for any ST313 strain. “Despite being one of the best characterized pathogens, we still have limited knowledge of the mechanisms used by Salmonella to cause disease in humans, including the multidrug-resistant ST313 isolates associated with rampant atypical disease and high mortality in sub-Saharan Africa,” Nickerson said. The new study offers insight into the model ST313 strain, D23580, which shows both key similarities and differences between classic Typhimurium and Typhi strains in its virulence and pathogenesis-related properties, thus offering clues as to how it may cause disease in humans. Salmonella, a rod-shaped bacterium, infects a broad range of warm- and cold-blooded animals around the world. The pathogen has an aptitude for infection under varying conditions and a stubborn durability. It can survive freezing temperatures, the highly acidic conditions found in the human stomach, and the low oxygen and detergent-like bile stresses present in the intestine. Two broad categories of Salmonella — known as typhoidal and non-typhoidal — menace human populations. Strains of the former include Salmonella Typhi and S. Paratyphi and are responsible for typhoid fever. They are so-called host-restricted pathogens, targeting only humans and higher primates. S. Typhi flourishes under conditions of poor hygiene and is typically a problem in underdeveloped countries, where it is acquired by ingesting food or water contaminated with feces from an infected person. A vaccine for typhoid offers protection in approximately 50-70 percent of cases. The condition, if not successfully treated, can lead to shock, organ failure and death. Non-typhoidal forms of Salmonella are responsible for foodborne illness, sickening tens of millions worldwide each year in both developed and underdeveloped countries, according to the World Health Organization. In healthy individuals, the infection is self-limiting and restricted to the intestinal tract. There are more than 2,500 different variants of non-typhoidal Salmonella. Usually, non-typhoidal Salmonella are transmitted through the consumption of contaminated food, primarily meat, poultry, eggs and milk. Currently, there is no effective vaccine to protect against non-typhoidal Salmonella food poisoning. ST313 often does not produce symptoms of gastroenteritis typically associated with foodborne illness. Rather, invasive non-typhoidal Salmonella (iNTS) strains such as ST313 are a leading cause of bloodstream infections in sub-Saharan Africa, which are often fatal. In addition to causing high mortality, iNTS infections display resistance to multiple antibiotics, making effective treatment challenging, particularly in impoverished regions lacking access to effective alternatives. Team collaborators for the current project include Kenneth Roland, Rebecca Forsyth and Jacquelyn Kilbourne, (with the Biodesign Institute’s Center for Infectious Diseases and Vaccinology) and Mark Ott (with NASA’s Johnson Space Center).
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