Department of Microbiology and Molecular Medicine, University Medical Center, University of Geneva, 1211 Geneva 4, Switzerland.
Proc Natl Acad Sci U S A. 2010 Jun 29;107(26):11954-8. doi: 10.1073/pnas.1000489107. Epub 2010 Jun 14.
Staphylococcus aureus is an versatile pathogen that can cause life-threatening infections. Depending on the clinical setting, up to 50% of S. aureus infections are caused by methicillin-resistant strains (MRSA) that in most cases are resistant to many other antibiotics, making treatment difficult. The emergence of community-acquired MRSA drastically changed the picture by increasing the risk of MRSA infections. Horizontal transfer of genes encoding for antibiotic resistance or virulence factors is a major concern of multidrug-resistant S. aureus infections and epidemiology. We identified and characterized a type III-like restriction system present in clinical S. aureus strains that prevents transformation with DNA from other bacterial species. Interestingly, our analysis revealed that some clinical MRSA strains are deficient in this restriction system, and thus are hypersusceptible to the horizontal transfer of DNA from other species, such as Escherichia coli, and could easily acquire a vancomycin-resistance gene from enterococci. Inactivation of this restriction system dramatically increases the transformation efficiency of clinical S. aureus strains, opening the field of molecular genetic manipulation of these strains using DNA of exogenous origin.
金黄色葡萄球菌是一种多功能病原体，可以导致危及生命的感染。根据临床环境的不同，高达 50%的金黄色葡萄球菌感染是由耐甲氧西林金黄色葡萄球菌（MRSA）引起的，而这种细菌在大多数情况下对许多其他抗生素都具有耐药性，这使得治疗变得困难。社区获得性耐甲氧西林金黄色葡萄球菌的出现通过增加耐甲氧西林金黄色葡萄球菌感染的风险，极大地改变了这种情况。抗生素耐药性或毒力因子基因的水平转移是多药耐药性金黄色葡萄球菌感染和流行病学的主要关注点。我们在临床金黄色葡萄球菌株中发现并鉴定了一种 III 型样限制系统，该系统可防止来自其他细菌物种的 DNA 的转化。有趣的是，我们的分析表明，一些临床耐甲氧西林金黄色葡萄球菌株在这种限制系统中存在缺陷，因此对来自其他物种（如大肠杆菌）的 DNA 的水平转移非常敏感，并且可以很容易地从肠球菌获得万古霉素耐药基因。该限制系统的失活极大地提高了临床金黄色葡萄球菌株的转化效率，为使用外源性 DNA 对这些菌株进行分子遗传操作开辟了道路。
