Enterobacterial Common Antigen Mutants of Salmonella enterica Serovar Typhimurium Establish a Persistent Infection and Provide Protection against Subsequent Lethal Challenge
Enterobacterial Common Antigen Mutants of Salmonella enterica Serovar Typhimurium Establish a Persistent Infection and Provide Protection against Subsequent Lethal Challenge
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DOI：
10.1128/iai.05559-11
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发表时间：
2012-01-01
影响因子：
3.1
通讯作者：
Metcalf, Eleanor S.
中科院分区：
文献类型：
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作者：
Gilbreath, Jeremy J.;Dodds, Jennifer Colvocoresses;Metcalf, Eleanor S.
沙门氏菌属感染是全球疾病的一个重要来源。这些感染中有相当大比例是由肠道沙门氏菌血清型鼠伤寒沙门氏菌引起的。在此，我们阐述了肠杆菌共同抗原（ECA）在鼠伤寒沙门氏菌致病过程中的作用，ECA是一种在肠道细菌中普遍存在的表面糖脂。在两株具有临床相关性的鼠伤寒沙门氏菌菌株TML和SL1344中，对UDP - N - 乙酰葡糖胺 - 1 - 磷酸转移酶基因wecA构建一个确定的突变，导致菌株无法产生ECA。ECA的缺失并不影响细胞表面的总体超微结构、脂多糖（LPS）的产生、鞭毛或运动性。然而，wecA突变菌株在口服和腹腔注射小鼠感染模型中致病性均减弱（P<0.05）。在口服感染模型中，wecA突变体的半数致死量（LD50）比野生型菌株高10倍以上（P<0.001）。在腹腔注射感染模型中，wecA突变体的LD50比野生型菌株高约100倍（P<0.001）。此外，wecA突变体在脾脏和肝脏中的定殖能力显著降低（P<0.001），并且在脾脏和肝脏中的细菌载量比野生型菌株低100 - 1000倍。这些结果表明，ECA在鼠伤寒沙门氏菌的致病性中起着重要作用，并且可能是开发新型抗菌策略的一个潜在靶点。
Infection with Salmonella spp. is a significant source of disease globally. A substantial proportion of these infections are caused by Salmonella enterica serovar Typhimurium. Here, we characterize the role of the enterobacterial common antigen (ECA), a surface glycolipid ubiquitous among enteric bacteria, in S. Typhimurium pathogenesis. Construction of a defined mutation in the UDP-N-acetylglucosamine-1-phosphate transferase gene, wecA, in two clinically relevant strains of S. Typhimurium, TML and SL1344, resulted in strains that were unable to produce ECA. Loss of ECA did not affect the gross cell surface ultrastructure, production of lipopolysaccharide (LPS), flagella, or motility. However, the wecA mutant strains were attenuated in both oral and intraperitoneal mouse models of infection (P