期刊
ACS INFECTIOUS DISEASES
卷 4, 期 6, 页码 860-867出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsinfecdis.8b00105
关键词
bacteria; cell wall; lytic transglycosylases; antibiotic resistance; beta-lactam antibiotics
资金
- NIH [GM61629, AI113219]
- postdoctoral fellowship from the Uehara Memorial Foundation
- NIH Training Grant [T32GM075762]
- ECK Institute for Global Health
The bulgecins are iminosaccharide secondary metabolites of the Gram-negative bacterium Paraburkholderia acidophila and inhibitors of lytic transglycosylases of bacterial cell-wall biosynthesis and remodeling. The activities of the bulgecins are intimately intertwined with the mechanism of a cobiosynthesized beta-lactam antibiotic. beta-Lactams inhibit the penicillin-binding proteins, enzymes also critical to cell-wall biosynthesis. The simultaneous loss of the lytic transglycosylase (by bulgecin) and penicillin-binding protein (by beta-lactams) activities results in deformation of the septal cell wall, observed microscopically as a bulge preceding bacterial cell lysis. We describe a practical synthesis of the three naturally occurring bulgecin iminosaccharides and their mechanistic evaluation in a series of microbiological studies. These studies identify potentiation by the bulgecin at subminimum inhibitory concentrations of the beta-lactam against three pathogenic Gram-negative bacteria and establish for the first time that this potentiation results in a significant increase in the bactericidal efficacy of a clinical beta-lactam.
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