Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, NY 13244, USA.
Appl Environ Microbiol. 2010 Mar;76(6):1967-74. doi: 10.1128/AEM.02321-09. Epub 2010 Jan 22.
Biofilms are sessile microbial communities that cause serious chronic infections with high morbidity and mortality. In order to develop more effective approaches for biofilm control, a series of linear cationic antimicrobial peptides (AMPs) with various arginine (Arg or R) and tryptophan (Trp or W) repeats [(RW)(n)-NH(2), where n = 2, 3, or 4] were rigorously compared to correlate their structures with antimicrobial activities affecting the planktonic growth and biofilm formation of Escherichia coli. The chain length of AMPs appears to be important for inhibition of bacterial planktonic growth, since the hexameric and octameric peptides significantly inhibited E. coli growth, while tetrameric peptide did not cause noticeable inhibition. In addition, all AMPs except the tetrameric peptide significantly reduced E. coli biofilm surface coverage and the viability of biofilm cells, when added at inoculation. In addition to inhibition of biofilm formation, significant killing of biofilm cells was observed after a 3-hour treatment of preformed biofilms with hexameric peptide. Interestingly, treatment with the octameric peptide caused significant biofilm dispersion without apparent killing of biofilm cells that remained on the surface; e.g., the surface coverage was reduced by 91.5 + or - 3.5% by 200 microM octameric peptide. The detached biofilm cells, however, were effectively killed by this peptide. Overall, these results suggest that hexameric and octameric peptides are potent inhibitors of both bacterial planktonic growth and biofilm formation, while the octameric peptide can also disperse existing biofilms and kill the detached cells. These results are helpful for designing novel biofilm inhibitors and developing more effective therapeutic methods.
生物膜是一种定殖的微生物群落,可导致严重的慢性感染,具有高发病率和死亡率。为了开发更有效的生物膜控制方法,我们严格比较了一系列具有不同精氨酸(Arg 或 R)和色氨酸(Trp 或 W)重复的线性阳离子抗菌肽(AMP)[(RW)(n)-NH(2),其中 n = 2、3 或 4],以将其结构与影响大肠杆菌浮游生长和生物膜形成的抗菌活性相关联。AMP 的链长对于抑制细菌浮游生长似乎很重要,因为六聚体和八聚体肽显著抑制大肠杆菌生长,而四聚体肽则不会引起明显的抑制。此外,除了四聚体肽外,所有 AMP 都在接种时显著降低了大肠杆菌生物膜表面覆盖率和生物膜细胞的活力。除了抑制生物膜形成外,在用六聚体肽处理预先形成的生物膜 3 小时后,还观察到生物膜细胞的显著杀伤。有趣的是,用八聚体肽处理会导致生物膜明显分散,而表面上残留的生物膜细胞没有明显的杀伤;例如,用 200 μM 八聚体肽处理可使表面覆盖率降低 91.5±3.5%。然而,该肽可有效杀死脱落的生物膜细胞。总体而言,这些结果表明六聚体和八聚体肽是细菌浮游生长和生物膜形成的有效抑制剂,而八聚体肽还可以分散现有的生物膜并杀死脱落的细胞。这些结果有助于设计新型生物膜抑制剂和开发更有效的治疗方法。