Virulence and vaccine potential of Salmonella typhimurium mutants deficient in the expression of the RpoS (sigma (S)) regulon
Virulence and vaccine potential of Salmonella typhimurium mutants deficient in the expression of the RpoS (sigma (S)) regulon
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DOI：
10.1111/j.1365-2958.1996.tb02664.x
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发表时间：
1996-10-01
影响因子：
3.6
通讯作者：
Norel, F
中科院分区：
文献类型：
--
作者：
Coynault, C;RobbeSaule, V;Norel, F
备选西格玛因子RpoS（西格玛(S)）是沙门氏菌在小鼠中的毒力所必需的。我们报道了鼠伤寒沙门菌rpoS和rpoS aroA突变体的免疫能力，以保护易感的BALB/c小鼠免受毒力鼠伤寒沙门菌的后续口服攻击。当口服或腹腔注射小鼠毒力鼠伤寒沙门氏菌菌株C52和SL1344的rpoS衍生物时，它们是高度减毒的，是有效的单剂量活疫苗。经口服或腹腔注射后评估，rpoS aroA突变体比相应的单一aroA或rpoS突变体更弱，但保留了显著的保护小鼠免受沙门氏菌病侵害的能力。因此，沙门氏菌rpoS和rpoS aroA突变体在合理的疫苗设计中值得认真考虑。与此相一致的是，Ty2伤寒沙门氏菌——一种广泛用于开发人类伤寒候选活疫苗的“野生型”菌株——被证明对rpoS有缺陷。此外，我们的研究结果表明，rpoS不仅控制鼠伤寒沙门氏菌在深部淋巴器官的生长和持续，而且在口腔感染的初始阶段发挥作用。
The alternative sigma factor RpoS (sigma(S)) is required for Salmonella virulence in mice. We report the immunizing capacity of Salmonella typhimurium rpoS and rpoS aroA mutants to protect susceptible BALB/c mice against subsequent oral challenge with virulent S. typhimurium. When administered orally or intraperitoneally, rpoS derivatives of the mouse-virulent S. typhimurium strains, C52 and SL1344, were highly attenuated and were efficient single-dose live vaccines. rpoS aroA mutants were more attenuated than corresponding single aroA or rpoS mutants, as assessed after oral or intraperitoneal administration, but retained significant ability to protect mice against salmonellosis. Salmonella rpoS and rpoS aroA mutants therefore deserve serious consideration for rational vaccine design. Consistent with this, Salmonella typhi Ty2, a 'wild-type' strain used widely for the development of human live-vaccine candidates against typhoid fever, was shown to be defective for rpoS. In addition, our results demonstrate that rpoS not only controls the growth and persistence of S. typhimurium in deep lymphoid organs, but also plays a role during the initial stages of oral infection.