ZmpB, a novel virulence factor of Streptococcus pneumoniae that induces tumor necrosis factor alpha production in the respiratory tract

被引:51
作者
Blue, CE
Paterson, GK
Kerr, AR
Bergé, M
Claverys, JP
Mitchell, TJ
机构
[1] Univ Glasgow, Div Infect & Immun, Inst Biomed & Life Sci, Glasgow G12 8QQ, Lanark, Scotland
[2] Univ Toulouse 3, CNRS, Lab Microbiol & Genet Mol, F-31062 Toulouse, France
关键词
D O I
10.1128/IAI.71.9.4925-4935.2003
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Inflammation is a prominent feature of Streptococcus pneumoniae infection in both humans and animal models. Indeed, an intense host immune response to infection is thought to contribute significantly to the pathology of pneumococcal pneumonia and meningitis. Previously, induction of the inflammatory response following infection with S. pneumoniae has been attributed to certain cell wall constituents and the toxin pneumolysin. Here we present data implicating a putative zinc metalloprotease, ZmpB, as having a role in inflammation. Null mutations were created in the zmpB gene of the virulent serotype 2 strain D39 and analyzed in a murine model of infection. Isogenic mutants were attenuated in pneumonia and septicemia models of infection, as determined by levels of bacteremia and murine survival. Mutants were not attenuated in colonization of murine airways or lung tissue. Examination of cytokine profiles within the lung tissue revealed significantly lower levels of the proinflammatory cytokine tumor necrosis factor alpha following challenge with the DeltazmpB mutant (Delta739). These data identify ZmpB as a novel virulence factor capable of inducing inflammation in the lower respiratory tract. The possibility that ZmpB was involved in inhibition of complement activity was examined, but the data indicated that ZmpB does not have a significant effect on this important host defense. The regulation of ZmpB by a two-component system (TCS09) located immediately upstream of the zmpB gene was examined. TCS09 was not required for the expression of zmpB during exponential growth in vitro.
引用
收藏
页码:4925 / 4935
页数:11
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