Virulence of invasive <i>Salmonella</i> Typhimurium ST313 in animal models of infection

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.鼠伤寒沙门氏菌（Salmonella Typhimurium）序列型（sequence type, ST）313可导致撒哈拉以南非洲婴儿罹患败血症。现有研究已明确ST313菌株与胃肠炎相关的ST19菌株存在遗传与表型差异，但针对ST313菌株体内毒力的相关报道数据存在冲突。为解决这些分歧，我们在小鼠与恒河猴感染模型中测试了临床分离的鼠伤寒沙门氏菌ST313与ST19菌株。 我们测定了3株鼠伤寒沙门氏菌ST19及ST313菌株对小鼠的半数致死量（LD50）。在细菌播散研究中，我们检测了攻毒后不同时间点小鼠各器官内的细菌载量。我们使用1株ST19菌株与1株ST313菌株感染印度恒河猴，对受试动物开展临床症状监测，并测定其细菌载量与病理变化。 ST19与ST313感染小鼠的LD50值无显著差异。但感染24小时后，ST313感染的BALB/c小鼠血液中的细菌载量显著高于ST19感染小鼠。感染ST19的恒河猴表现为中重度腹泻，而ST313感染的猴只出现无或轻度腹泻。ST19感染的猴组织内细菌载量更高，炎症反应也更为显著。 本研究数据表明，可通过小鼠模型开展鼠伤寒沙门氏菌ST313的侵袭性研究。非人灵长类实验结果与临床数据一致，提示ST313菌株不会引发腹泻。