RpoS co-operates with other factors to induce Legionella pneumophila virulence in the stationary phase

RpoS co-operates with other factors to induce Legionella pneumophila virulence in the stationary phase
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DOI:
10.1046/j.1365-2958.2001.02465.x
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发表时间:
2001-06-01
影响因子:
3.6
通讯作者:
Swanson, MS
Swanson, MS
中科院分区:
生物学2区
文献类型:
--
作者:
Bachman, MA;Swanson, MS

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嗜肺军团菌在阿米巴和巨噬细胞内复制,引起严重的肺炎。当肉汤培养物进入指数后生长(PE)期或经历氨基酸限制时,L。嗜肺菌积累严格响应信号(p)ppGpp并表达可能促进传递至新吞噬细胞的性状。严格反应机制调节L.我们发现无毒突变体Lp 120在编码稳定期σ因子RpoS的基因中含有内部缺失,这支持了嗜肺菌毒力。为了直接测试RpoS是否与稳定期协同毒力,构建并分析了同基因野生型、rpoS-120和rpoS无效突变株。PE相L. pneumophila通过RpoS非依赖性途径变得具有细胞毒性,但它们的钠敏感性和鞭毛蛋白的最大表达需要RpoS。同样,通过实验诱导的(p)ppGpp合成完全诱导钠敏感性需要RpoS。为了在巨噬细胞中有效复制,L. pneumophila使用Rpos依赖性和非依赖性途径。像那些含有dotA IV型分泌器突变体,吞噬体窝藏rpoS或dotA rpoS突变体迅速收购晚期内体蛋白LAMP-1,但不是溶酶体标记得克萨斯红卵清蛋白。总之,这些数据支持一个模型,在该模型中,RpoS与其他监管机构合作,以诱导L。在PE阶段的嗜肺菌毒力。
Legionella pneumophila replicates within amoebae and macrophages and causes the severe pneumonia Legionnaires' disease. When broth cultures enter the post-exponential growth (PE) phase or experience amino acid limitation, L. pneumophila accumulates the stringent response signal (p)ppGpp and expresses traits likely to promote transmission to a new phagocyte. The hypothesis that a stringent response mechanism regulates L. pneumophila virulence was bolstered by our finding that the avirulent mutant Lp120 contains an internal deletion in the gene encoding the stationary phase sigma factor RpoS. To test directly whether RpoS co-ordinates virulence with stationary phase, isogenic wild-type, rpoS-120 and rpoS null mutant strains were constructed and analysed. PE phase L. pneumophila became cytotoxic by an RpoS-independent pathway, but their sodium sensitivity and maximal expression of flagellin required RpoS. Likewise, full induction of sodium sensitivity by experimentally induced (p)ppGpp synthesis required RpoS. To replicate efficiently in macrophages, L. pneumophila used both RpoS-dependent and -independent pathways. Like those containing the dotA type IV secretory apparatus mutant, phagosomes harbouring either rpoS or dotA rpoS mutants rapidly acquired the late endosomal protein LAMP-1, but not the lysosomal marker Texas red-ovalbumin. Together, the data support a model in which RpoS co-operates with other regulators to induce L. pneumophila virulence in the PE phase.