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.
Highlights
Salmonella enterica serovar Typhimurium generally causes gastroenteritis in immunocompetent individuals
Salmonella Typhimurium ST313 models and RS) NIH/NIAID Centers for Excellence in Translation Research grant U19 AI109776-01 awarded to MML
Kingsley et al [4] compared the genome of an ST313 strain, D23580, from Malawi, with the genomes of Salmonella Typhimurium ST19 gastroenteritis-associated strains and observed that D23580 appeared to have undergone genome degradation similar to what has been observed for Salmonella Typhi and Paratyphi A [6]
Summary
Salmonella enterica serovar Typhimurium generally causes gastroenteritis in immunocompetent individuals. There is growing evidence to suggest that in certain susceptible populations, such as infants in sub-Saharan Africa and HIV-positive adults, Salmonella Typhimurium infection manifests as septicemia without any gastroenteritis [1,2,3]. There is a novel genotype of Salmonella Typhimurium circulating in Africa called sequence type (ST) 313 (based on multi-locus sequence typing) [4]. Okoro et al [7] further describe two lineages of invasive Salmonella Typhimurium, lineage I and lineage II, which emerged at the same time as HIV in Africa. The authors hypothesize that lineage I isolates have been replaced by lineage II isolates due to the use of chloramphenicol for treatment of invasive non-typhoidal Salmonella (iNTS)
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