Majcherczyk Paul A, Barblan Jean-Luc, Moreillon Philippe, Entenza José M
Department of Fundamental Microbiology, Faculty of Biology and Medicine, University of Lausanne, CH-1015 Lausanne, Switzerland.
Microb Pathog. 2008 Nov-Dec;45(5-6):408-14. doi: 10.1016/j.micpath.2008.09.003. Epub 2008 Sep 27.
Glycopeptide-intermediate resistant Staphylococcus aureus (GISA) are characterized by multiple changes in the cell wall and an altered expression of global virulence regulators. We investigated whether GISA are affected in their infectivity in a rat model of experimental endocarditis. The glycopeptide-susceptible, methicillin-resistant S. aureus M1V2 and its laboratory-derived GISA M1V16 were examined for their ability to (i) adhere to fibrinogen and fibronectin in vitro, (ii) persist in the bloodstream after intravenous inoculation, (iii) colonize aortic vegetations in rats, and (iv) compete for valve colonization by co-inoculation. Both GISA M1V16 and M1V2 adhered similarly to fibrinogen and fibronectin in vitro. In rats, GISA M1V16 was cleared faster from the blood (P < 0.05) and required 100-times more bacteria than parent M1V2 (10(6) versus 10(4)CFU) to infect 90% of vegetations. GISA M1V16 also had 100 to 1000-times lower bacterial densities in vegetations. Moreover, after co-inoculation with GISA M1V16 and M1V2Rif, a rifampin-resistant variant of M1V2 to discriminate them in organ cultures, GISA M1V16 was out-competed by the glycopeptide-susceptible counterpart. Thus, in rats with experimental endocarditis, GISA showed an attenuated virulence, likely due to a faster clearance from the blood and a reduced fitness in cardiac vegetations. The GISA phenotype appeared globally detrimental to infectivity.
糖肽类中介耐药金黄色葡萄球菌（GISA）的特征是细胞壁发生多种变化以及全局毒力调节因子的表达改变。我们研究了GISA在实验性心内膜炎大鼠模型中的感染性是否受到影响。检测了糖肽类敏感、耐甲氧西林金黄色葡萄球菌M1V2及其实验室衍生的GISA M1V16在以下方面的能力：（i）体外黏附纤维蛋白原和纤连蛋白；（ii）静脉接种后在血流中持续存在；（iii）在大鼠主动脉赘生物中定植；（iv）通过共同接种竞争瓣膜定植。GISA M1V16和M1V2在体外对纤维蛋白原和纤连蛋白的黏附情况相似。在大鼠中，GISA M1V16从血液中清除得更快（P < 0.05），感染90%的赘生物所需的细菌数量比亲本M1V2多100倍（10⁶对10⁴CFU）。GISA M1V16在赘生物中的细菌密度也低100至1000倍。此外，在与GISA M1V16和M1V2Rif（M1V2的耐利福平变体，用于在器官培养中区分它们）共同接种后，GISA M1V16被糖肽类敏感的对应菌株竞争淘汰。因此，在患有实验性心内膜炎的大鼠中，GISA显示出毒力减弱，可能是由于从血液中清除更快以及在心脏赘生物中的适应性降低。GISA表型总体上似乎对感染性不利。
