人抗菌肽 LL-37 及其片段对多重耐药鲍曼不动杆菌具有抗菌和抗生物膜活性。
The human antimicrobial peptide LL-37 and its fragments possess both antimicrobial and antibiofilm activities against multidrug-resistant Acinetobacter baumannii.
机构信息
Department of Wound Infections, Bacterial Diseases Branch, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA.
出版信息
Peptides. 2013 Nov;49:131-7. doi: 10.1016/j.peptides.2013.09.007. Epub 2013 Sep 23.
Acinetobacter baumannii infections are difficult to treat due to multidrug resistance. Biofilm formation by A. baumannii is an additional factor in its ability to resist antimicrobial therapy. The antibacterial and antibiofilm activities of the human antimicrobial peptide LL-37 and its fragments KS-30, KR-20 and KR-12 against clinical isolates of multidrug-resistant (MDR) A. baumannii were evaluated. The minimal inhibitory concentration (MIC) of LL-37 against MDR A. baumannii isolates ranged from 16 to 32 μg/mL. The MIC of KS-30 fragment varied from 8.0 to 16 μg/mL and the KR-20 fragment MIC ranged from 16 to 64 μg/mL. LL-37 and KS-30 fragment exhibited 100% bactericidal activity against five A. baumannii strains, including four MDR clinical isolates, within 30 min at concentrations of 0.25-1 μg/mL. By 0.5h, the fragments KR-20 and KR-12 eliminated all tested strains at 8 and 64 μg/mL respectively. LL-37 and its fragments displayed anti-adherence activities between 32-128 μg/mL. A minimum biofilm eradication concentration (MBEC) biofilm assay demonstrated that LL-37 inhibited and dispersed A. baumannii biofilms at 32 μg/mL respectively. Truncated fragments of LL-37 inhibited biofilms at concentrations of 64-128 μg/mL. KS-30, the truncated variant of LL-37, effectively dispersed biofilms at 64 μg/mL. At 24h, no detectable toxicity was observed at the efficacious doses when cytotoxicity assays were performed. Thus, LL-37, KS-30 and KR-20 exhibit significant antimicrobial activity against MDR A. baumannii. The prevention of biofilm formation in vitro by LL-37, KS-30 and KR-20 adds significance to their efficacy. These peptides can be potential therapeutics against MDR A. baumannii infections.
鲍曼不动杆菌感染由于其多重耐药性而难以治疗。鲍曼不动杆菌生物膜的形成是其抵抗抗菌治疗的另一个因素。评估了人抗菌肽 LL-37 及其片段 KS-30、KR-20 和 KR-12 对临床分离的多重耐药（MDR）鲍曼不动杆菌的抗菌和抗生物膜活性。LL-37 对 MDR 鲍曼不动杆菌分离株的最小抑菌浓度（MIC）范围为 16 至 32 μg/mL。KS-30 片段的 MIC 从 8.0 到 16 μg/mL 不等，KR-20 片段的 MIC 范围从 16 到 64 μg/mL。在浓度为 0.25-1 μg/mL 时，LL-37 和 KS-30 片段在 30 分钟内对包括四个 MDR 临床分离株在内的五株鲍曼不动杆菌菌株表现出 100%的杀菌活性。在 0.5 小时时，片段 KR-20 和 KR-12 分别在 8 和 64 μg/mL 时消除了所有测试菌株。LL-37 和其片段在 32-128 μg/mL 之间显示出抗黏附活性。最低生物膜消除浓度（MBEC）生物膜测定表明，LL-37 以 32 μg/mL 的浓度分别抑制和分散鲍曼不动杆菌生物膜。LL-37 的截断片段在 64-128 μg/mL 的浓度下抑制生物膜。KS-30，LL-37 的截断变体，以 64 μg/mL 的浓度有效分散生物膜。在 24 小时时，当进行细胞毒性测定时，在有效剂量下未观察到可检测的毒性。因此，LL-37、KS-30 和 KR-20 对 MDR 鲍曼不动杆菌表现出显著的抗菌活性。LL-37、KS-30 和 KR-20 在体外抑制生物膜形成的能力增加了它们的疗效。这些肽可以成为治疗 MDR 鲍曼不动杆菌感染的潜在治疗方法。
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