Salmonella is an infectious agent with many faces, appearing in a multitude of strains affecting animals and humans. A distinct form of the bacterial invader has emerged in sub-Saharan Africa and is responsible for severe epidemic outbreaks.
Its unusual characteristics — including a high rate of lethality, invasiveness, atypical symptomatolgy and resistance to multiple antibiotics — are of rising concern.
In a new study, Cheryl Nickerson and her colleagues at the Biodesign Institute at Arizona State University and NASA Johnson Space Center demonstrate for the first time that this pathogen can cause lethal infections not only in humans but in mice, a finding which could potentially extend to other hosts as well.
The salmonella strain used in this study, D23580, belongs to a group of closely related strains collectively known as ST313, and was shown to more rapidly reach and colonize tissues of the spleen and gallbladder in mice, compared with a well-characterized “classic” salmonella strain.
In results appearing in the journal PLOS Neglected Tropical Diseases, lead authors Jiseon Yang and Jennifer Barrila also establish 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.
Developing effective means to diagnose and treat deadly salmonella infections, including those caused by ST313, will require a more thorough understanding of the strategies used by such pathogens to infect the body. Establishing LD50 is a necessary step for examining the trajectory of salmonella infection and developing effective vaccines and therapies to combat it.
“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,” said Nickerson, who is also a professor of microbiology at ASU’s School of Life Sciences.
The current study offers new insight into the virulence and pathogenesis properties of 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.
Thus far, no animal reservoir has been identified for ST313. Unlike conventional foodborne NTS infections, the transmission route for ST313 appears to be human-to-human. Genetic studies of iNTS strains obtained from Malawi, where ST313 is highly prevalent; indicate the strain may be losing genetic diversity, becoming a more specialized pathogen, similar to S. Typhi.
The current study, however, shows that ST313 strain D23580 could also infect mice and thus retains characteristics associated with classic NTS infection. However, biochemical and phenotypic assays indicated that D23580 also exhibits important differences between classic NTS and typhoidal strains. Collectively, these results provide further evidence that this emerging pathogen is distinct from classic salmonella strains.