Mutation of luxS affects growth and virulence factor expression in Streptococcus pyogenes
Mutation of luxS affects growth and virulence factor expression in Streptococcus pyogenes
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DOI：
10.1046/j.1365-2958.2001.02616.x
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发表时间：
2001-10-01
影响因子：
3.6
通讯作者：
Caparon, MG
中科院分区：
文献类型：
--
作者：
Lyon, WR;Madden, JC;Caparon, MG
细菌的适应性反应包括感知其他细菌的存在，这对细菌的增殖和毒力特征的表达通常是至关重要的。最近证明，自身诱导物II(AI-2)途径是一种感知其他细菌的机制，在不同的细菌物种中高度保守，包括革兰氏阳性病原体。然而，这一途径在革兰氏阳性病原体毒力因子调节中的作用尚未确定。在本研究中，我们在革兰氏阳性病原菌化脓性链球菌中灭活了AI-2途径的重要组成部分LuxS。对产生的突变体的分析表明，几种毒力特性的异常表达受到生长期的调节，包括溶血活性增强，以及分泌的蛋白分解活性的表达显著降低。后一种缺陷与半胱氨酸蛋白酶前体(SpeB)的分泌和处理能力降低以及该酶表达的时间不同有关。LUXS菌株的溶血活性增强也与溶血素S相关基因SagA的表达增加有关。这些突变体中LUXS的中断也产生了依赖于介质的生长缺陷。最后，化脓性链球菌的等位基因替换分析表明，在感染过程中调节毒力的机制是在LuxS中自然插入IS 1239。本研究结果表明，LUXS在化脓性链球菌毒力因子的调控中起着重要作用。
Adaptive responses of bacteria that involve sensing the presence of other bacteria are often critical for proliferation and the expression of virulence characteristics. The autoinducer II (AI-2) pathway has recently been shown to be a mechanism for sensing other bacteria that is highly conserved among diverse bacterial species, including Gram-positive pathogens. However, a role for this pathway in the regulation of virulence factors in Gram-positive pathogens has yet to be established. In this study, we have inactivated luxS, an essential component of the AI-2 pathway, in the Gram-positive pathogen Streptococcus pyogenes. Analyses of the resulting mutants revealed the aberrant expression of several virulence properties that are regulated in response to growth phase, including enhanced haemolytic activity, and a dramatic reduction in the expression of secreted proteolytic activity. This latter defect was associated with a reduced ability to secrete and process the precursor of the cysteine protease (SpeB) as well as a difference in the timing of expression of the protease. Enhanced haemolytic activity of the luxS strain was also shown to be linked with an increased expression of the haemolysin S-associated gene sagA. Disruptions of luxS in these mutants also produced a media-dependent growth defect. Finally, an allelic replacement analysis of an S. pyogenes strain with a naturally occurring insertion of IS 1239 in luxS suggested a mechanism for modulation of virulence during infection. Results from this study suggest that luxS makes an important contribution to the regulation of S. pyogenes virulence factors.