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功能定义 LuxS,一种自动诱导物-2(AI-2)合酶及其在猪链球菌 2 型完全毒力中的作用。

Functional definition of LuxS, an autoinducer-2 (AI-2) synthase and its role in full virulence of Streptococcus suis serotype 2.

机构信息

Department of Microbiology, Third Military Medical University, Chongqing, P. R. China.

出版信息

J Microbiol. 2011 Dec;49(6):1000-11. doi: 10.1007/s12275-011-1523-1. Epub 2011 Dec 28.

DOI:10.1007/s12275-011-1523-1
PMID:22203565
Abstract

Quorum sensing is a widespread chemical communication in response to fluctuation of bacterial population density, and has been implicated into bacterial biofilm formation and regulation of expression of virulence factors. The luxS gene product, S-ribosylhomocysteinase, catalizes the last committed step in biosynthetic pathway of autoinducer 2 (AI-2), a signaling molecule for inter-species quorum sensing. We found a luxS homologue in 05ZYH33, an epidemic strain of Streptococcus suis serotype 2 (SS2) in China. A luxS null mutant (ΔluxS) of 05ZYH33 strain was obtained using an approach of homologous recombination. LuxS was determined to be required for AI-2 production in 05ZYH33 strain of S. suis 2. Inactivation of luxS gene led to a wide range of phenotypic changes including thinner capsular walls, increased tolerance to H(2)O(2), reduced adherence capacity to epithelial cells, etc. In particular, loss of LuxS impaired dramatically its full virulence of SS2 in experimental model of piglets, and functional complementation restored it nearly to the level of parent strain. Genome-wide transcriptome analyses suggested that some known virulence factors such as CPS are down-regulated in the ΔluxS mutant, which might in part explain virulence attenuation by luxS deletion. Similarly, 29 of 71 genes with different expression level were proposed to be targets candidate regulated by LuxS/AI-2-dependent quorum sensing.

摘要

群体感应是一种广泛存在的化学通讯方式,对细菌种群密度的波动有响应,并与细菌生物膜的形成和毒力因子的表达调控有关。LuxS 基因产物 S- 核酮糖 1,5-二磷酸羟甲基转移酶催化了自动诱导物 2(AI-2)生物合成途径中的最后一个关键步骤,AI-2 是一种种间群体感应的信号分子。我们在中国流行的猪链球菌 2 型(SS2)血清型菌株 05ZYH33 中发现了一个 luxS 同源物。通过同源重组的方法获得了 05ZYH33 菌株的 luxS 缺失突变体(ΔluxS)。LuxS 被确定是 SS2 05ZYH33 菌株 AI-2 产生所必需的。LuxS 基因的失活导致了广泛的表型变化,包括荚膜壁变薄、对 H2O2 的耐受性增加、对上皮细胞的黏附能力降低等。特别是,LuxS 的缺失极大地损害了 SS2 在仔猪实验模型中的完全毒力,而功能互补几乎恢复了亲本菌株的水平。全基因组转录组分析表明,一些已知的毒力因子,如 CPS,在 ΔluxS 突变体中下调,这可能部分解释了 luxS 缺失导致的毒力衰减。类似地,71 个具有不同表达水平的基因中有 29 个被认为是受 LuxS/AI-2 依赖的群体感应调控的候选靶标。

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