Antimicrobial Activity of Community-associated Methicillin-resistant Staphylococcus aureus Is Caused by Phenol-soluble Modulin Derivatives
Antimicrobial Activity of Community-associated Methicillin-resistant Staphylococcus aureus Is Caused by Phenol-soluble Modulin Derivatives
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DOI：
10.1074/jbc.m111.221382
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发表时间：
2011-03-18
影响因子：
4.8
通讯作者：
Otto, Michael
中科院分区：
文献类型：
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作者：
Joo, Hwang-Soo;Cheung, Gordon Y. C.;Otto, Michael
社区相关的耐甲氧西林金黄色葡萄球菌（CA-MRSA）正在引起主要是皮肤和软组织感染的持续大流行。CA-MRSA作为病原体的成功是由于抗生素耐药性与高毒力的结合。此外，据推测，CA-MRSA菌株，如流行的美国克隆USA300，由于基于细菌素的细菌干扰，增加了定殖人上皮细胞的能力。我们在此分析了在金黄色葡萄球菌菌株中检测到的抗菌活性的分子基础，包括那些USA300谱系。与之前的假设相反，我们发现这种活性不是由于抗生素型细菌素的表达，而是由于酚溶性调节素（PSM）肽PSM α 1和PSM α 2的蛋白水解处理衍生物。值得注意的是，加工后的PSM α 1和PSM α 2对化脓性链球菌表现出相当大的活性，这表明PSM在干扰金黄色葡萄球菌菌株与竞争定殖病原体的作用。此外，通过在人体定植过程中提供竞争优势，USA300和其他CA-MRSA菌株中psm的高产量可能不仅有助于毒力，而且还有助于这些菌株在人群中持续传播的特殊能力，迄今为止人们对这一点知之甚少。
Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) are causing an ongoing pandemic of mostly skin and soft tissue infections. The success of CA-MRSA as pathogens is due to a combination of antibiotic resistance with high virulence. In addition, it has been speculated that CA-MRSA strains such as the epidemic U. S. clone USA300 have increased capacity to colonize human epithelia, owing to bacteriocin-based bacterial interference. We here analyzed the molecular basis of antimicrobial activity detected in S. aureus strains, including those of the USA300 lineage. In contrast to a previous hypothesis, we found that this activity is not due to expression of a lantibiotic-type bacteriocin, but proteolytically processed derivatives of the phenol-soluble modulin (PSM) peptides PSM alpha 1 and PSM alpha 2. Notably, processed PSM alpha 1 and PSM alpha 2 exhibited considerable activity against Streptococcus pyogenes, indicating a role of PSMs in the interference of S. aureus strains with the competing colonizing pathogen. Furthermore, by offering a competitive advantage during colonization of the human body, the characteristically high production of PSMs in USA300 and other CA-MRSA strains may thus contribute not only to virulence but also the exceptional capacity of those strains to sustainably spread in the population, which so far has remained poorly understood.