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.

非伤寒沙门氏菌（Nontyphoidal Salmonella）是全球广泛传播的病原菌，也是胃肠炎的主要致病原。沙门氏菌病的发病机制已通过体内鼠类感染模型以及通常以鼠伤寒沙门氏菌（Salmonella Typhimurium）为感染攻击对象的细胞系得到广泛研究。尽管肠炎沙门氏菌（Salmonella Enteritidis）和鼠伤寒沙门氏菌是美国疾控中心（CDC）报告的人类感染病例中占比最高的致病血清型，但其余多种血清型同样可引发沙门氏菌病的临床病例。尽管这些血清型具有重要的流行病学意义，但人们对其感染表型仍知之甚少。本研究报道了与美国多州食源性暴发疫情相关的10株非典型肠道沙门氏菌（S. enterica）血清型的毒力特征及其基因组序列。我们证实，鼠源RAW 264.7巨噬细胞感染模型并不适用于推断非伤寒沙门氏菌感染中与人类感染相关的差异，而经分化的人源THP-1巨噬细胞则可在更贴合人类生理的感染环境中，对这些沙门氏菌分离株开展进一步的特征分析。