Human host defense peptide LL-37 prevents bacterial biofilm formation
Human host defense peptide LL-37 prevents bacterial biofilm formation
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DOI：
10.1128/iai.00318-08
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发表时间：
2008-09-01
影响因子：
3.1
通讯作者：
Hancock, Robert E. W.
中科院分区：
文献类型：
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作者：
Overhage, Joerg;Campisano, Andrea;Hancock, Robert E. W.
形成生物膜的能力是铜绿假单胞菌慢性感染的关键因素，并且使该细菌成为生物膜形成的模式生物。这项研究描述了一个新的，以前未被认识到的作用，为人类阳离子宿主防御肽LL-37。除了其在调节先天免疫应答中的关键作用和弱的抗微生物活性外，LL-37还在体外有效地抑制细菌生物膜的形成。这发生在0.5 μ g/ml的非常低且具有生理意义的浓度下，远低于杀死或抑制生长所需的浓度（MIC = 64 μ g/ml）。LL-37还影响现有的预生长铜绿假单胞菌生物膜。使用牛嗜中性粒细胞肽indolicidin获得了类似的结果，但是使用亚抑制浓度的小鼠肽CRAMP（其与LL-37、多粘菌素B或牛bactenecin同系物Bac 2A具有67%的同一性）未检测到对生物膜形成的抑制作用。使用微阵列和后续研究，我们能够证明LL-37通过减少细菌细胞的附着，刺激抽搐运动，并影响两个主要的群体感应系统（Las和Rhl），导致生物膜发育所必需的基因下调，从而影响生物膜形成。
The ability to form biofilms is a critical factor in chronic infections by Pseudomonas aeruginosa and has made this bacterium a model organism with respect to biofilm formation. This study describes a new, previously unrecognized role for the human cationic host defense peptide LL-37. In addition to its key role in modulating the innate immune response and weak antimicrobial activity, LL-37 potently inhibited the formation of bacterial biofilms in vitro. This occurred at the very low and physiologically meaningful concentration of 0.5 mu g/ml, far below that required to kill or inhibit growth (MIC = 64 mu g/ml). LL-37 also affected existing, pregrown P. aeruginosa biofilms. Similar results were obtained using the bovine neutrophil peptide indolicidin, but no inhibitory effect on biofilm formation was detected using subinhibitory concentrations of the mouse peptide CRAMP, which shares 67% identity with LL-37, polymyxin B, or the bovine bactenecin homolog Bac2A. Using microarrays and follow-up studies, we were able to demonstrate that LL-37 affected biofilm formation by decreasing the attachment of bacterial cells, stimulating twitching motility, and influencing two major quorum sensing systems (Las and Rhl), leading to the downregulation of genes essential for biofilm development.