万古霉素是最后防线的抗生素,已有十几株金黄色葡萄球菌对其产生耐受,研究人员测定了这些耐受菌的基因组序列,结果显示:每株菌独立地出现耐药性,有一些共同特征,从而有助于它们获得万古霉素抗性和逃避人类系统免疫防御。
在美国,耐甲氧西林金黄色葡萄球菌(MRSA)是医院内获得性感染的一种主要病因,最新数据显示,它在2005年引起1.8万人死亡。严重的多重耐药性MRSA感染需要用万古霉素治疗。从2002年以来,在美国已记录有12例耐万古霉素金黄色葡萄球菌(VRSA)的病例,这使人们更加担心,如果万古霉素耐受变得普遍,葡萄球菌感染可能无法治疗。大多数VRSA情况发生在肢体感染的糖尿病患者,以存在多种类型细菌为特点,包括万古霉素耐受的肠球菌。
该研究比较了这12株VRSA的遗传差别,最后发现,它们的共同祖先出现在50多年以前,正好在万古霉素耐受出现之前;万古霉素耐受不是在人与人之间传播,而是重复出现在每例VRSA病例里;每一株VRSA菌株获得一点称为转座子Tn1546的遗传物质。
所有VRSA菌株都属于葡萄球菌的CC5家族或CC5进化枝,而CC5进化枝通常见于抗生素耐受的医院内获得性感染,缺乏制造天然抗生素定居因子的能力,这就是它们为什么能与肠球菌共存的原因。CC5菌株能制造一些蛋白质,这些蛋白质可瓦解人大量的免疫应答而使细菌兴旺发达,从而增强混合感染中耐受因子从肠球菌转移至葡萄球菌的优势。
为什么VRSA的人与人传播没有变得普遍?基因组也提供了相关线索,CC5菌株没有制造或抵制抗生素殖民化因子的能力,在遇到任何天然出现的葡萄球菌时处于劣势,因为天然出现的葡萄球菌通常生活在皮肤上,能产生抗生素定居因子。(生物谷bioon.com)
doi:10.1128/mBio.00112-12
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Comparative genomics of vancomycin-resistant Staphylococcus aureus strains and their positions within the clade most commonly associated with methicillin-resistant S. aureus hospital-acquired infection in the United States
Veronica N. Kos, Christopher A. Desjardins, Allison Griggs, Gustavo Cerqueira, Andries Van Tonder, Matthew T. G. Holden, Paul Godfrey, Kelli L. Palmer, Kip Bodi, Emmanuel F. Mongodin, Jennifer Wortman, Michael Feldgarden, Trevor Lawley, Steven R. Gill, Brian J. Haas, Bruce Birren and Michael S. Gilmore
Methicillin-resistant Staphylococcus aureus (MRSA) strains are leading causes of hospital-acquired infections in the United States, and clonal cluster 5 (CC5) is the predominant lineage responsible for these infections. Since 2002, there have been 12 cases of vancomycin-resistant S. aureus (VRSA) infection in the United States-all CC5 strains. To understand this genetic background and what distinguishes it from other lineages, we generated and analyzed high-quality draft genome sequences for all available VRSA strains. Sequence comparisons show unambiguously that each strain independently acquired Tn1546 and that all VRSA strains last shared a common ancestor over 50 years ago, well before the occurrence of vancomycin resistance in this species. In contrast to existing hypotheses on what predisposes this lineage to acquire Tn1546, the barrier posed by restriction systems appears to be intact in most VRSA strains. However, VRSA (and other CC5) strains were found to possess a constellation of traits that appears to be optimized for proliferation in precisely the types of polymicrobic infection where transfer could occur. They lack a bacteriocin operon that would be predicted to limit the occurrence of non-CC5 strains in mixed infection and harbor a cluster of unique superantigens and lipoproteins to confound host immunity. A frameshift in dprA, which in other microbes influences uptake of foreign DNA, may also make this lineage conducive to foreign DNA acquisition.