Atypical Salmonella enterica serovars in murine and human infection models: Is it time to reassess our approach to the study of salmonellosis?

Nontyphoidal <i>Salmonella </i>species<i> </i>are globally disseminated pathogens and the predominant cause of gastroenteritis. The pathogenesis of salmonellosis has been extensively studied using <i>in vivo</i> murine models and cell lines typically challenged with <i>Salmonella</i> Typhimurium. Although<i> </i>serovars Enteritidis and Typhimurium are responsible for the most<i> </i>of human infections reported to the CDC, several other serovars also contribute to clinical cases of salmonellosis. Despite their epidemiological importance, little is known about their infection phenotypes. Here, we report the virulence characteristics and genomes of 10 atypical <i>S. enterica</i> serovars linked to multistate foodborne outbreaks in the United States. We show that the murine RAW 264.7 macrophage<i> </i>model of infection is unsuitable for inferring human relevant differences in nontyphoidal <i>Salmonella </i>infections<i> </i>whereas differentiated human THP-1 macrophages allowed these isolates to be further characterised in a more relevant, human context.