Inhibition of Bacterial Biofilm Formation and Swarming Motility by a Small Synthetic Cationic Peptide
Inhibition of Bacterial Biofilm Formation and Swarming Motility by a Small Synthetic Cationic Peptide
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DOI：
10.1128/aac.00064-12
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发表时间：
2012-05-01
影响因子：
4.9
通讯作者：
Hancock, Robert E. W.
中科院分区：
文献类型：
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作者：
de la Fuente-Nunez, Cesar;Korolik, Victoria;Hancock, Robert E. W.
生物膜引起高达80%的感染，并且由于与它们的抗生素对应物相比它们具有实质性的多药耐药性而难以治疗。基于人肽LL-37能够在低于其MIC的浓度下阻断生物膜形成的观察结果，我们筛选了具有生物膜活性的小肽，并鉴定了长度仅为9个氨基酸的新型合成阳离子肽1037。肽1037具有非常弱的抗微生物活性，但在1/30的MIC下，肽能够有效地防止革兰氏阴性病原体铜绿假单胞菌和新洋葱伯克霍尔德氏菌以及革兰氏阳性单核细胞增生李斯特菌的生物膜形成（细胞生物量减少>50%）。使用流动池系统和宽视野荧光显微镜，显示1037显著减少生物膜形成并导致生物膜中的细胞死亡。微阵列和后续研究表明，在铜绿假单胞菌中，1037通过减少游泳和群集运动、刺激抽搐运动和抑制参与生物膜形成的多种基因的表达来直接抑制生物膜（例如，例如，在一个实施例中，PA 2204）。来自用肽LL-37和1037处理的细胞的微阵列数据的比较使得能够鉴定11种常见的铜绿假单胞菌基因，这些基因在生物膜形成中具有作用，并且被提议代表这些肽的功能靶标。肽1037显示出作为针对由多种细菌引起的慢性、复发性生物膜感染的潜在治疗剂的前景。
Biofilms cause up to 80% of infections and are difficult to treat due to their substantial multidrug resistance compared to their planktonic counterparts. Based on the observation that human peptide LL-37 is able to block biofilm formation at concentrations below its MIC, we screened for small peptides with antibiofilm activity and identified novel synthetic cationic peptide 1037 of only 9 amino acids in length. Peptide 1037 had very weak antimicrobial activity, but at 1/30th the MIC the peptide was able to effectively prevent biofilm formation (>50% reduction in cell biomass) by the Gram-negative pathogens Pseudomonas aeruginosa and Burkholderia cenocepacia and Gram-positive Listeria monocytogenes. Using a flow cell system and a widefield fluorescence microscope, 1037 was shown to significantly reduce biofilm formation and lead to cell death in biofilms. Microarray and follow-up studies showed that, in P. aeruginosa, 1037 directly inhibited biofilms by reducing swimming and swarming motilities, stimulating twitching motility, and suppressing the expression of a variety of genes involved in biofilm formation (e. g., PA2204). Comparison of microarray data from cells treated with peptides LL-37 and 1037 enabled the identification of 11 common P. aeruginosa genes that have a role in biofilm formation and are proposed to represent functional targets of these peptides. Peptide 1037 shows promise as a potential therapeutic agent against chronic, recurrent biofilm infections caused by a variety of bacteria.