Lyon W R, Madden J C, Levin J C, Stein J L, Caparon M G
Department of Molecular Microbiology, Washington University School of Medicine, Box 8230, St Louis, MO 63110-1093, USA.
Mol Microbiol. 2001 Oct;42(1):145-57. doi: 10.1046/j.1365-2958.2001.02616.x.
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 IS1239 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.
细菌的适应性反应涉及感知其他细菌的存在，这通常对其增殖和毒力特征的表达至关重要。最近研究表明，自诱导物II（AI-2）途径是一种在包括革兰氏阳性病原体在内的多种细菌物种中高度保守的感知其他细菌的机制。然而，该途径在革兰氏阳性病原体毒力因子调控中的作用尚未明确。在本研究中，我们使革兰氏阳性病原体化脓性链球菌中的AI-2途径的必需成分luxS失活。对所得突变体的分析揭示了几种受生长阶段调控的毒力特性的异常表达，包括溶血活性增强，以及分泌性蛋白水解活性的表达显著降低。后一种缺陷与半胱氨酸蛋白酶（SpeB）前体的分泌和加工能力降低以及蛋白酶表达时间的差异有关。luxS突变株溶血活性增强还与溶血素S相关基因sagA的表达增加有关。这些突变体中luxS的破坏还导致了培养基依赖性生长缺陷。最后，对luxS中自然存在IS1239插入的化脓性链球菌菌株进行等位基因置换分析，提示了感染期间毒力调节的机制。本研究结果表明，luxS对化脓性链球菌毒力因子的调控起重要作用。
