Synergistic Effects and Antibiofilm Properties of Chimeric Peptides against Multidrug-Resistant Acinetobacter baumannii Strains
Synergistic Effects and Antibiofilm Properties of Chimeric Peptides against Multidrug-Resistant Acinetobacter baumannii Strains
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DOI：
10.1128/aac.02473-13
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发表时间：
2014-03-01
影响因子：
4.9
通讯作者：
Park, Yoonkyung
中科院分区：
文献类型：
--
作者：
Gopal, Ramamourthy;Kim, Young Gwon;Park, Yoonkyung
耐药病原体的日益流行凸显了识别新型抗生素的必要性。在这里，我们研究了四种新型抗菌肽（AMP）对潜在药物开发的功效。四种嵌合 AMP 的抗菌活性、协同效应和抗生物膜特性针对鲍曼不动杆菌（一种新兴的革兰氏阴性、医院内耐药病原体）进行了测试。一家医院从胆石症患者体内分离出 19 株对氨苄西林、头孢噻肟、环丙沙星、妥布霉素和红霉素耐药的鲍曼不动杆菌。所有四种肽对所有 19 种菌株均表现出显着的抗菌作用（MIC = 3.12 至 12.5 muM），而五种商业抗生素对相同病原体几乎没有或没有活性。多粘菌素是一个例外，它对所有测试的菌株都有效。当与头孢噻肟、环丙沙星或红霉素联合施用时，每种肽都显示出针对一种或多种菌株的协同作用。这些肽还表现出防止生物膜形成的能力，而头孢噻肟、环丙沙星或红霉素则没有观察到这种能力，但多粘菌素也能抑制生物膜形成。事实上，当与环丙沙星联合给药时，AMP HPMA 对鲍曼不动杆菌生物膜的形成发挥了有效的协同作用。总的来说，我们的研究结果表明，所测试的 AMP 没有细胞毒性，但具有有效的抗菌和抗生物膜活性，并且可能与商业抗生素产生协同作用。
The increasing prevalence of drug-resistant pathogens highlights the need to identify novel antibiotics. Here we investigated the efficacies of four new antimicrobial peptides (AMPs) for potential drug development. The antibacterial activities, synergistic effects, and antibiofilm properties of the four chimeric AMPs were tested against Acinetobacter baumannii, an emerging Gram-negative, nosocomial, drug-resistant pathogen. Nineteen A. baumannii strains resistant to ampicillin, cefotaxime, ciprofloxacin, tobramycin, and erythromycin were isolated at a hospital from patients with cholelithiasis. All four peptides exhibited significant antibacterial effects (MIC = 3.12 to 12.5 mu M) against all 19 strains, whereas five commercial antibiotics showed little or no activity against the same pathogens. An exception was polymyxin, which was effective against all of the strains tested. Each of the peptides showed synergy against one or more strains when administered in combination with cefotaxime, ciprofloxacin, or erythromycin. The peptides also exhibited an ability to prevent biofilm formation, which was not seen with cefotaxime, ciprofloxacin, or erythromycin, though polymyxin also inhibited biofilm formation. Indeed, when administered in combination with ciprofloxacin, the AMP HPMA exerted a potent synergistic effect against A. baumannii biofilm formation. Collectively, our findings indicate that the AMPs tested have no cytotoxicity but possess potent antibacterial and antibiofilm activities and may act synergistically with commercial antibiotics.