Virulence of invasive Salmonella Typhimurium ST313 in animal models of infection

Abstract

Salmonella Typhimurium sequence type (ST) 313 produces septicemia in infants in sub-Saharan Africa. Although there are known genetic and phenotypic differences between ST313 strains and gastroenteritis-associated ST19 strains, conflicting data about the in vivo virulence of ST313 strains have been reported. To resolve these differences, we tested clinical Salmonella Typhimurium ST313 and ST19 strains in murine and rhesus macaque infection models. The 50% lethal dose (LD50) was determined for three Salmonella Typhimurium ST19 and ST313 strains in mice. For dissemination studies, bacterial burden in organs was determined at various time-points post-challenge. Indian rhesus macaques were infected with one ST19 and one ST313 strain. Animals were monitored for clinical signs and bacterial burden and pathology were determined. The LD50 values for ST19 and ST313 infected mice were not significantly different. However, ST313-infected BALB/c mice had significantly higher bacterial numbers in blood at 24 h than ST19-infected mice. ST19-infected rhesus macaques exhibited moderate-to-severe diarrhea while ST313-infected monkeys showed no-to-mild diarrhea. ST19-infected monkeys had higher bacterial burden and increased inflammation in tissues. Our data suggest that Salmonella Typhimurium ST313 invasiveness may be investigated using mice. The non-human primate results are consistent with clinical data, suggesting that ST313 strains do not cause diarrhea.

Machine learning identifies signatures of host adaptation in the bacterial pathogen Salmonella enterica

“…Lineage II appears to have largely replaced Lineage I since 2004, and it has been suggested this is due to Lineage II possessing a gene encoding chloramphenicol resistance [ 47 ]. Laboratory characterization of Lineage II strains has shown that they are not host-restricted [ 52 , 53 ], but do appear to possess characteristics suggestive of adaptation to an invasive lifestyle [ 54 – 57 ], though it is important to note that this is a complex trait and not easily quantified.…”

Defective Phagocytic Properties of HIV-Infected Macrophages: How Might They Be Implicated in the Development of Invasive Salmonella Typhimurium?

“…Mice are not typically suitable as an adapted model for S. Typhimurium, as these bacteria induce a typhoid-like systemic illness that leads to death of the animals. Although the 50% lethal dose (LD 50 ) was not reported to be significantly different between ST313- and ST19-infected mice ( 87 , 93 ). Further, there was no consistent difference in the inflammatory response ( 79 , 88 , 93 , 126 ) or in the ability of the bacteria to colonize the intestinal tract and to disseminate in the body ( 79 , 87 , 88 , 92 , 93 , 126 ).…”

“…In addition, several ST313 strains express less flagellin, a component of the flagellum appendage responsible for bacterial motility ( 91 , 92 ). Indeed, ST313 strains (D65, Q55, S11, S12, D23580, and A130) were reported to be less motile than ST19 strains (I77, I89, I41, S52, and SL1344) ( 91 , 93 ), although some variability among the strains was observed ( 87 ). These data suggest that, like Salmonella Typhi, Salmonella Typhimurium ST313 lack some of the mechanisms that allow transmission and/or survival in the environment.…”

Genome Variation and Molecular Epidemiology of Salmonella enterica Serovar Typhimurium Pathovariants

“…Experimental infections of mice and primates largely support the view that ST313 strains have altered pathogenicity compared with those of commonly used laboratory strains, such as strains SL1344 and ATCC 14028. An ST313 isolate hyperdisseminated from the intestine to systemic sites in the murine model of infection and in poultry ( 16 , 17 , 53 ). Furthermore, ST313 strains exhibit decreases in intestinal pathology in mice, fluid accumulation and migration of inflammatory cells to the intestinal lumen in bovine ileal loops, and diarrhea in rhesus macaques ( 53 , 54 ).…”