期刊
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
卷 67, 期 9, 页码 2173-2181出版社
OXFORD UNIV PRESS
DOI: 10.1093/jac/dks174
关键词
-barrel assembly machinery complex; combination effect; outer membrane protein
资金
- Toho University Graduate School of Medicine [22-27]
- Tokai University School of Medicine
- Research and Study Project of the Tokai University Educational System General Research Organization
- Grants-in-Aid for Scientific Research [22133002] Funding Source: KAKEN
The -barrel assembly machinery (BAM) complex plays a critical role in outer membrane protein (OMP) biogenesis. The outer membrane (OM) of Pseudomonas aeruginosa is centrally involved in mechanisms of antibiotic resistance. This study aimed to identify effects of a synthetic peptide based on conserved sequences in the putative BamA-binding region of BamD, focusing on antibiotic susceptibility and OMP characteristics in P. aeruginosa. We synthesized a peptide FIRL (Phe-Ile-Arg-Leu-CONH2) with a sequence related to that of the BamD protein. We assessed antibiotic susceptibility of P. aeruginosa PAO1 using the chequerboard method and a timekill assay. Changes in OMPs and in OM permeability were examined using SDS-PAGE, western blot analysis and nitrocefin assays. The combined effects of the peptide and antibiotics were investigated using a mouse pneumonia model. Although the peptide alone exerted no antimicrobial effect, it reduced the MICs of colistin, levofloxacin, erythromycin, vancomycin and rifampicin for P. aeruginosa PAO1 by 4-fold or more. Timekill tests revealed bacterial numbers were significantly reduced after 2 h of incubation with the peptide plus colistin or levofloxacin. Moreover, in the presence of the peptide, expression of OprM was reduced by a third, and OM permeability was increased. The combination of the peptide (2.08 mg/kg) and colistin (1.25 mg/kg) significantly reduced P. aeruginosa by more than 1 log cfu/mL in a mouse pneumonia model. We show, for the first time, that a synthetic peptide based on homologous sequences of BamD can potentiate antibiotic susceptibility of P. aeruginosa.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据