Li Gui-qiu, Quan Feng, Qu Ting, Lu Juan, Chen Shu-lan, Cui Lan-ying, Guo Da-wen, Wang Yong-chen
Department of Laboratory Diagnosis, the first Affiliated Hospital of Harbin Medical University, No. 194, Rd. Xuefu, District Nangang, Harbin, 150081, Heilongjiang Province, China.
Department of Rheumatology, the Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, Heilongjiang Province, China.
Biosci Rep. 2015 Sep 30;35(6):e00279. doi: 10.1042/BSR20140167.
Staphylococcus aureus is the leading cause of many human infectious diseases. Besides infectious dangers, S. aureus is well-known for the quickly developed drug resistance. Although great efforts have been made, mechanisms underlying the antibiotic effects of S. aureus are still not well clarified. Recently, reports have shown that oxidative stress connects with bactericidal antibiotics [Dwyer et al. (2009) Curr. Opin. Microbiol. 12: , 482-489]. Based on this point, we demonstrate that reactive oxygen species (ROS) induced by sublethal vancomycin may be partly responsible for the antibiotic resistance in heterogeneous vancomycin resistant S. aureus (hVRSA). Sublethal vancomycin treatment may induce protective ROS productions in hVRSA, whereas reduction in ROS level in hVRSA strains may increase their vancomycin susceptibility. Moreover, low dose of ROS in VSSA (vancomycin susceptible S. aureus) strains may promote their survival under vancomycin conditions. Our findings reveal that modest ROS generation may be protective for vancomycin resistance in hVRSA. These results recover novel insights into the relationship between oxidative stress and bacterial resistance, which has important applications for further use of antibiotics and development of therapeutics strategies for hVRSA.
金黄色葡萄球菌是许多人类传染病的主要病因。除了具有感染危险性外，金黄色葡萄球菌还因其迅速产生的耐药性而闻名。尽管已经做出了巨大努力，但金黄色葡萄球菌对抗生素产生作用的机制仍未得到很好的阐明。最近，有报道表明氧化应激与杀菌性抗生素有关[德怀尔等人（2009年），《微生物学当前观点》12卷：，482 - 489页]。基于这一点，我们证明亚致死剂量的万古霉素诱导产生的活性氧（ROS）可能部分导致了异质性万古霉素耐药金黄色葡萄球菌（hVRSA）的抗生素耐药性。亚致死剂量的万古霉素处理可能会在hVRSA中诱导产生保护性的ROS，而hVRSA菌株中ROS水平的降低可能会增加它们对万古霉素的敏感性。此外，在万古霉素敏感金黄色葡萄球菌（VSSA）菌株中低剂量的ROS可能会促进它们在万古霉素环境下的存活。我们的研究结果表明适度产生ROS可能对hVRSA的万古霉素耐药性具有保护作用。这些结果为氧化应激与细菌耐药性之间的关系提供了新的见解，这对于抗生素的进一步应用以及hVRSA治疗策略的开发具有重要意义。
