Quantitative proteomic view associated with resistance to clinically important antibiotics in Gram-positive bacteria: a systematic review.
Quantitative proteomic view associated with resistance to clinically important antibiotics in Gram-positive bacteria: a systematic review.
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DOI：
10.3389/fmicb.2015.00828
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发表时间：
2015
影响因子：
5.2
通讯作者：
Lee SH
中科院分区：
文献类型：
--
作者：
Lee CR;Lee JH;Park KS;Jeong BC;Lee SH
耐甲氧西林金黄色葡萄球菌(MRSA)和耐万古霉素肠球菌(VRE)的增加对世界范围内的健康构成严重威胁。尽管已经开发了新的抗生素，如达托霉素和利奈唑胺，用于治疗革兰氏阳性病原体的感染，但治疗过程中出现的达托霉素耐药株和利奈唑胺耐药株现在增加了临床治疗失败的次数。在过去的几年里，使用定量蛋白质组学方法的研究在理解抗生素耐药机制方面取得了相当大的进展。为了解临床上治疗革兰氏阳性菌的4种重要抗生素(甲氧西林、万古霉素、利奈唑胺和达托霉素)的耐药机制，本文综述了应用定量蛋白质组学方法研究耐药机制的最新进展，并对在细菌对4种抗生素耐药机制中起重要作用的蛋白质进行了分析。蛋白质组学研究可以确定在单一抗生素耐药机制中表达水平发生变化的蛋白质，如达托霉素耐药中的Liah和万古霉素耐药中的PrSA，而多个蛋白质同时参与多种抗生素的耐药机制。大多数耐药相关蛋白同时与多种抗生素的耐药机制相关，在调节细菌包膜生物发生或补偿抗生素耐药的适宜性成本方面发挥着重要作用。因此，蛋白质组学数据证实，抗生素耐药性需要适应成本，而细菌被膜是抗生素耐药性的重要因素。
The increase of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) poses a worldwide and serious health threat. Although new antibiotics, such as daptomycin and linezolid, have been developed for the treatment of infections of Gram-positive pathogens, the emergence of daptomycin-resistant and linezolid-resistant strains during therapy has now increased clinical treatment failures. In the past few years, studies using quantitative proteomic methods have provided a considerable progress in understanding antibiotic resistance mechanisms. In this review, to understand the resistance mechanisms to four clinically important antibiotics (methicillin, vancomycin, linezolid, and daptomycin) used in the treatment of Gram-positive pathogens, we summarize recent advances in studies on resistance mechanisms using quantitative proteomic methods, and also examine proteins playing an important role in the bacterial mechanisms of resistance to the four antibiotics. Proteomic researches can identify proteins whose expression levels are changed in the resistance mechanism to only one antibiotic, such as LiaH in daptomycin resistance and PrsA in vancomycin resistance, and many proteins simultaneously involved in resistance mechanisms to various antibiotics. Most of resistance-related proteins, which are simultaneously associated with resistance mechanisms to several antibiotics, play important roles in regulating bacterial envelope biogenesis, or compensating for the fitness cost of antibiotic resistance. Therefore, proteomic data confirm that antibiotic resistance requires the fitness cost and the bacterial envelope is an important factor in antibiotic resistance.