Bismuth antimicrobial drugs serve as broad-spectrum metallo-β-lactamase inhibitors

• Published in: Nature communications Vol. 9; no. 1; pp. 439 - 12
• Main Authors: Wang, Runming, Lai, Tsz-Pui, Gao, Peng, Zhang, Hongmin, Ho, Pak-Leung, Woo, Patrick Chiu-Yat, Ma, Guixing, Kao, Richard Yi-Tsun, Li, Hongyan, Sun, Hongzhe
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30.01.2018; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 140/131; 140/58; 38/77; 631/154/1435; 631/326/22; 631/45/173; 64/60; 82/80; 82/83; Animals; Anti-Infective Agents - chemistry; Anti-Infective Agents - pharmacology; Antibiotics; Antimicrobial agents; Bacteria; Bacterial diseases; beta-Lactam Resistance - drug effects; beta-Lactamase Inhibitors - pharmacology; beta-Lactamases - chemistry; beta-Lactamases - metabolism; Bismuth; Bismuth - chemistry; Bismuth - metabolism; Bismuth - pharmacology; Bismuth compounds; Carbapenems; Carbapenems - pharmacology; Catalytic Domain; Cofactors; Crystallography; Crystallography, X-Ray; Dogs; Drug Evaluation, Preclinical - methods; Drug resistance; Evolution, Molecular; Female; Helicobacter pylori; Humanities and Social Sciences; Inhibitors; Madin Darby Canine Kidney Cells - drug effects; Meropenem; Metallo-β-lactamase; Metallography; Mice, Inbred BALB C; Microbial Sensitivity Tests; multidisciplinary; Organometallic Compounds - chemistry; Organometallic Compounds - pharmacology; Peritonitis - drug therapy; Peritonitis - microbiology; Science; Science (multidisciplinary); X-ray crystallography; Zinc - metabolism

Drug-resistant superbugs pose a huge threat to human health. Infections by Enterobacteriaceae producing metallo-β-lactamases (MBLs), e.g., New Delhi metallo-β-lactamase 1 (NDM-1) are very difficult to treat. Development of effective MBL inhibitors to revive the efficacy of existing antibiotics is hi...