Cationic amphiphilic alpha-helical peptides for the treatment of carbapenem-resistant Acinetobacter baumannii infection
Cationic amphiphilic alpha-helical peptides for the treatment of carbapenem-resistant Acinetobacter baumannii infection
复制标题
用于治疗碳青霉烯类耐药鲍曼不动杆菌感染的阳离子两亲性α螺旋肽
DOI：
10.1016/j.biomaterials.2012.08.026
复制
发表时间：
2012-12-01
期刊：
影响因子：
14
通讯作者：
Fan, Weimin
中科院分区：
文献类型：
--
作者：
Huang, Yuan;Wiradharma, Nikken;Fan, Weimin
多重耐药革兰氏阴性菌的出现，特别是鲍曼不动杆菌和铜绿假单胞菌，是世界范围内的关键临床问题。抗菌肽（Antimicrobial peptides，AMPS）因其具有克服多重耐药菌的能力而受到越来越多的关注。我们最近报道了半胱氨酸官能化的α-螺旋肽LLKKLLKKC和CLLKKLLKKC在体外有效地根除革兰氏阴性菌。在这项研究中，这些肽对碳青霉烯类耐药的临床分离的A。在体外和体内研究了鲍曼不动杆菌。对20株临床分离的碳青霉烯类耐药株进行了最小抑菌浓度（MIC）测定。鲍曼不动杆菌与亚胺培南比较。结果表明，A.鲍曼不动杆菌对（LLKK）（2）C的敏感性高于对C（LLKK）（2）C的敏感性，20株鲍曼不动杆菌中90%的MIC分别小于或等于36.8 μ mol/L和63.1 μ mol/L。但C（LLKK）（2）C的杀菌效果比（LLKK）（2）C快得多。此外，这些肽在由碳青霉烯类耐药A.鲍曼不动杆菌。重要的是，两种肽都具有高治疗指数（>25），但对肝脏和肾脏功能以及血液中电解质的平衡没有显著的不良影响。这些肽可能是传统抗生素治疗由多重耐药革兰氏阴性菌引起的医院细菌感染的有希望的替代治疗模式，特别是碳青霉烯类耐药A。鲍曼不动杆菌。(C)2012爱思唯尔有限公司保留所有权利。
The emergence of multidrug-resistant Gram-negative bacteria, in particular Acinetobacter baumannii and Pseudomonas aeruginosa, is a critical clinical problem worldwide. Antimicrobial peptides (AMPS) have received increasing attention due to their ability to overcome multidrug-resistant microbes. We recently reported that cysteine-functionalized alpha-helical peptides LLKKLLKKC and CLLKKLLKKC effectively eradicated Gram-negative bacteria in vitro. In this study, the antibacterial properties of these peptides against carbapenem-resistant clinical isolates of A. baumannii were studied both in vitro and in vivo. The minimum inhibitory concentrations (MICs) of the peptides against 20 clinical isolates of carbapenem-resistant A. baumannii were determined in comparison with imipenem. The results showed that the A. baumannii isolates were more susceptible to (LLKK)(2)C than to C(LLKK)(2)C in vitro, and 90% of the 20 tested strains had an MIC of lower than or equal to 36.8 and 63.1 mu mol/L, respectively. However, the bactericidal effect of C(LLKK)(2)C was much faster than that of (LLKK)(2)C. Furthermore, these peptides also showed excellent potency in mouse models of peritonitis and pneumonia infections caused by carbapenem-resistant A. baumannii. Importantly, both peptides had a high therapeutic index (>25), but caused no significant adverse effects on the liver and kidney functions and the balance of electrolytes in the blood. These peptides can be a promising alternative treatment modality to traditional antibiotics for nosocomial bacterial infections caused by multidrug-resistant Gram-negative bacteria, especially carbapenem-resistant A. baumannii. (C) 2012 Elsevier Ltd. All rights reserved.