美国科学家的一项最新研究，揭开了“超级细菌”横行霸道的作用机制。他们发现，这类抗药性最强、最为凶残的金黄色葡萄球菌(S. aureus)能通过释放一种致命的“分子炸弹”，摧毁人体免疫系统。相关论文11月9日在线发表于《自然—医学》上。
抗药性金黄色葡萄球菌(MRSA)可以抵抗最强力的抗生素和药物，并能够引起各种感染，因此也被称为“超级细菌”(Superbug)。美国每年因“超级细菌”导致的死亡人数可达到18000例，超过了2005年美国死于艾滋病的16000人。同时，感染“超级细菌”的人数也在越来越多，1974年感染葡萄球菌的人中只有2%是MRSA，而到了2003年，这一数字达到了64%。感染“超级细菌”后的症状包括丘疹、肺炎等。
在最新的研究中，美国国立过敏和传染病研究所(NIAID)的微生物学家Michael Otto和同事发现，MRSA可以产生一类酚可溶性蛋白(PSMs)，这赋予了它们强大的威力。值得注意的是，这很可能是MRSA众多“诡计”的其中之一。
Otto的小组在实验室中培育出了一些PSM分子，并且将其应用于人类嗜中性粒细胞(neutrophil，一种人类免疫细胞，人体抵御葡萄球菌的第一道防线)。结果发现，数分钟后，这些免疫细胞开始变平，一个小时后，许多免疫细胞都遭到破坏。Otto表示，“我们认为，这就是金黄色葡萄球菌摆脱主要‘敌人’的方式。”
研究人员还对医院和社区获得性MRSA菌系进行了对比研究。尽管后者比前者抵抗的药物种类略少，但却更加凶残，往往在数天内就能致人于死地。研究结果表明，几种社区获得性MRSA菌系能够制造更多的PSM，而大多数的医院菌系并不制造该蛋白。研究人员认为，这可能就是社区获得性MRSA威力更加强大的原因。
进一步的研究证实了这一观点。当研究人员移除与编码PSM相关的基因后，社区获得性MRSA对小鼠的威胁程度降低，同时在小鼠皮肤上留下的脓肿块也较少。
美国加州大学旧金山分校的微生物学家和医师Henry Chambers表示，尽管PSM对理解社区获得性MRSA十分重要，但它只是“冰山一角”。“认为葡萄球菌具有‘一刀切’的机制是一种天真的想法，因为它们的种类太多了，”Chambers说。
Otto的小组正致力于创造PSM抗血清，并在小鼠身上进行试验。(科学网任霄鹏/编译)
原始出处:
Nature Medicine
Published online: 11 November 2007 | doi:10.1038/nm1656
Identification of novel cytolytic peptides as key virulence determinants for community-associated MRSA
Rong Wang1, Kevin R Braughton1, Dorothee Kretschmer2, Thanh-Huy L Bach1, Shu Y Queck1, Min Li1, Adam D Kennedy1, David W Dorward3, Seymour J Klebanoff4, Andreas Peschel2, Frank R DeLeo1 & Michael Otto1
Methicillin-resistant Staphylococcus aureus (MRSA) remains a major human pathogen. Traditionally, MRSA infections occurred exclusively in hospitals and were limited to immunocompromised patients or individuals with predisposing risk factors. However, recently there has been an alarming epidemic caused by community-associated (CA)-MRSA strains, which can cause severe infections that can result in necrotizing fasciitis or even death in otherwise healthy adults outside of healthcare settings1, 2. In the US, CA-MRSA is now the cause of the majority of infections that result in trips to the emergency room3. It is unclear what makes CA-MRSA strains more successful in causing human disease compared with their hospital-associated counterparts. Here we describe a class of secreted staphylococcal peptides that have a remarkable ability to recruit, activate and subsequently lyse human neutrophils, thus eliminating the main cellular defense against S. aureus infection. These peptides are produced at high concentrations by standard CA-MRSA strains and contribute significantly to the strains' ability to cause disease in animal models of infection. Our study reveals a previously uncharacterized set of S. aureus virulence factors that account at least in part for the enhanced virulence of CA-MRSA.
Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, 903 South 4th Street, Hamilton, Montana 59840, USA.
Cellular and Molecular Microbiology Unit, Medical Microbiology and Hygiene Department, University of Tübingen, Elfriede-Auhorn-Str. 6, 72076 Tübingen, Germany.
Microscopy Unit, Research Technologies Section, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, 903 South 4th Street, Hamilton, Montana 59840, USA.
Department of Medicine, University of Washington, 1959 Northeast Pacific Street, Seattle, Washington 98195, USA.
Correspondence to: Michael Otto1 e-mail: motto@niaid.nih.gov
