Mechanisms of polymyxin resistance: acquired and intrinsic resistance in bacteria.
Mechanisms of polymyxin resistance: acquired and intrinsic resistance in bacteria.
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DOI：
10.3389/fmicb.2014.00643
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发表时间：
2014
影响因子：
5.2
通讯作者：
Rolain JM
中科院分区：
文献类型：
--
作者：
Olaitan AO;Morand S;Rolain JM
多粘菌素是聚阳离子抗菌肽，是目前治疗多重耐药革兰氏阴性细菌感染的最后手段抗生素。重新引入多粘菌素用于抗菌治疗后，革兰氏阴性菌耐药性的报道有所增加。一些细菌，如肺炎克雷伯菌、铜绿假单胞菌和鲍曼不动杆菌，在称为获得性耐药的过程中对多粘菌素产生耐药性，而其他细菌，如变形杆菌属、沙雷氏菌属和伯克霍尔德氏菌属，对这些药物具有天然耐药性。临床分离株中多粘菌素耐药性的报告最近有所增加，包括获得性和固有耐药性病原体。这种增加被认为是一个严重的问题，由于目前可用的有效抗生素数量较少而引起人们的关注。这篇综述总结了有关细菌用来抵抗多粘菌素活性的不同策略的当前知识。革兰氏阴性菌采用多种策略来保护自己免受多粘菌素抗生素（多粘菌素B和粘菌素）的侵害，包括各种脂多糖（LPS）修饰，例如用磷酸乙醇胺和4-氨基-4-脱氧-L-阿拉伯糖修饰脂质A，此外还使用外排泵、形成荚膜和外膜蛋白OprH的过度表达，这些都在分子水平上得到有效调控。加深对这些机制的了解对于促进抗菌肽的研究和寻找针对临床相关革兰氏阴性菌的新的潜在药物至关重要且及时。
Polymyxins are polycationic antimicrobial peptides that are currently the last-resort antibiotics for the treatment of multidrug-resistant, Gram-negative bacterial infections. The reintroduction of polymyxins for antimicrobial therapy has been followed by an increase in reports of resistance among Gram-negative bacteria. Some bacteria, such as Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii, develop resistance to polymyxins in a process referred to as acquired resistance, whereas other bacteria, such as Proteus spp., Serratia spp., and Burkholderia spp., are naturally resistant to these drugs. Reports of polymyxin resistance in clinical isolates have recently increased, including acquired and intrinsically resistant pathogens. This increase is considered a serious issue, prompting concern due to the low number of currently available effective antibiotics. This review summarizes current knowledge concerning the different strategies bacteria employ to resist the activities of polymyxins. Gram-negative bacteria employ several strategies to protect themselves from polymyxin antibiotics (polymyxin B and colistin), including a variety of lipopolysaccharide (LPS) modifications, such as modifications of lipid A with phosphoethanolamine and 4-amino-4-deoxy-L-arabinose, in addition to the use of efflux pumps, the formation of capsules and overexpression of the outer membrane protein OprH, which are all effectively regulated at the molecular level. The increased understanding of these mechanisms is extremely vital and timely to facilitate studies of antimicrobial peptides and find new potential drugs targeting clinically relevant Gram-negative bacteria.
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