Abstract：
Salmonella Enteritidis (SE) can spread from the intestines to cause systemic infection, mainly involving macrophages. Intramacrophage Salmonella exits and reinfects neighboring cells, leading to severe disease. Salmonella genes involved in exiting from macrophages are not well understood or fully identified. A focA::Tn5 mutant was identified by an in vitro assay, with increased ability to exit from macrophages. A defined SEΔfocA mutant and its complemented derivative strain, SEΔfocA::focA, were constructed to confirm this phenotype. Although the lethal ability of focA mutants was similar to that of the parental SE in mice, it was isolated earlier from the liver and spleen than the parental SE. focA mutants induced higher levels of proinflammatory IL-12 and TNF-α compared with the parental SE and SEΔfocA::focA. focA mutants showed higher cytotoxicity and lower formate concentrations than SE and SEΔfocA::focA, whereas there was no change in pyroptosis, apoptosis and flagella formation ability. These current data suggest that the focA gene plays an important role in regulating intramacrophage Salmonella exiting and extraintestinal spread in mice, although the specific mechanism requires further in-depth studies.
摘要：
肠炎沙门氏菌（SE）可以从肠道传播引起全身感染，主要涉及巨噬细胞。嗜食性沙门氏菌排出并重新感染邻近细胞，导致严重的疾病。涉及从巨噬细胞中退出的沙门氏菌基因尚未被很好地理解或完全鉴定。通过体外测定鉴定了focA::Tn5突变体，从巨噬细胞退出的能力增强。定义的SEΔfocA突变体及其互补的衍生菌株，SEΔfocA::focA,被构建来证实这种表型。尽管focA突变体在小鼠中的致死能力与亲本SE相似，它比亲本SE更早地从肝脏和脾脏中分离。与亲本SE和SEΔfocA::focA相比，focA突变体诱导更高水平的促炎性IL-12和TNF-α。focA突变体显示出比SE和SEΔfocA::focA更高的细胞毒性和更低的甲酸盐浓度，而焦亡没有变化，细胞凋亡和鞭毛形成能力。这些最新数据表明，focA基因在调节小鼠体内沙门菌的排出和肠外传播中起着重要作用。尽管具体机制需要进一步深入研究。
