mBio：缺陷型金黄色葡萄球菌表现出特异性的抗生素选择性

刊登在国际杂志mBio上的一篇研究报告中，来自丹麦哥本哈根大学的研究者揭示了针对含有阴性群体感应系统的金黄色葡萄球菌的抗生素的选择。

金黄色葡萄球菌是人类机体中常见的一种共生菌，在某些条件下其可以转化成致病菌，引发致命性的感染。为了精细控制细菌的毒力，金葡菌开发出了一套agr群体感应系统，其通过胞外效应分子RNAIII来调节毒力基因的表达。

这项研究中，研究者阐述了agr操纵子的存在可以增强金葡菌对于RNAIII的表达，进而影响细菌的毒力表达情况。未来研究中，研究者希望深入研究，暴露在不死剂量的抗生素环丙沙、莫匹罗星及利福平下，细菌是否可以通过诱导RNAIII的表达来增加agr给细菌所带来的环境适应度及毒力。

研究者的研究结果阐述了为何从医院金葡菌感染换种分离出的agr缺陷菌株比较频繁，以及含有agr的金黄色葡萄球菌所表现出的对抗生素的适应性。

本文中，研究者Ingmer H说，我们发现了agr阴性的菌株相比agr阳性的菌株，在不死剂量抗生素的影响下所表现出较好的适应度，而且由于agr效应分子RNAIII的存在可以诱发agr阳性细胞出现适应度的缺失。这些结果可以帮助研究者解释，为何临床中总能够分离得到agr缺失的金葡菌菌株，这就为研究者开发新型的抵御金黄色葡萄球菌感染的疗法提供了新的思路。

doi:10.1128/mBio.00459-12
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Antibiotic-Mediated Selection of Quorum-Sensing-Negative Staphylococcus aureus.

Paulander W, Nissen Varming A, Bæk KT, Haaber J, Frees D, Ingmer H.

Staphylococcus aureus is a human commensal that at times turns into a serious bacterial pathogen causing life-threatening infections. For the delicate control of virulence, S. aureus employs the agr quorum-sensing system that, via the intracellular effector molecule RNAIII, regulates virulence gene expression. We demonstrate that the presence of the agr locus imposes a fitness cost on S. aureus that is mediated by the expression of RNAIII. Further, we show that exposure to sublethal levels of the antibiotics ciprofloxacin, mupirocin, and rifampin, each targeting separate cellular functions, markedly increases the agr-mediated fitness cost by inducing the expression of RNAIII. Thus, the extensive use of antibiotics in hospitals may explain why agr-negative variants are frequently isolated from hospital-acquired S. aureus infections but rarely found among community-acquired S. aureus strains. Importantly, agr deficiency correlates with increased duration of and mortality due to bacteremia during antibiotic treatment and with a higher frequency of glycopeptide resistance than in agr-carrying strains. Our results provide an explanation for the frequent isolation of agr-defective strains from hospital-acquired S. aureus infections and suggest that the adaptability of S. aureus to antibiotics involves the agr locus. IMPORTANCE Staphylococcus aureus is the most frequently isolated pathogen in intensive care units and a common cause of nosocomial infections, resulting in a high degree of morbidity and mortality. Surprisingly, a large fraction (15 to 60%) of hospital-isolated S. aureus strains are agr defective and lack the main quorum-sensing-controlled virulence regulatory system. This is a problem, as agr-defective strains are associated with a mortality level in bacteremic infections and a probability of glycopeptide resistance greater than those of other strains. We show here that agr-negative strains have a fitness advantage over agr-positive strains in the presence of sublethal concentrations of some antibiotics and that the fitness defect of agr-positive cells is caused by antibiotic-mediated expression of the agr effector molecule RNAIII. These results offer an explanation of the frequent isolation of agr-defective S. aureus strains in hospitals and will influence how we treat S. aureus infections.