期刊
NATURE CHEMICAL BIOLOGY
卷 12, 期 1, 页码 9-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nchembio.1950
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资金
- US Department of Energy (DOE), Office of Science, Office of Basic Energy Sciences [DE-AC02-76SF00515]
- DOE Office of Biological and Environmental Research
- US National Institutes of Health (NIH), National Institute of General Medical Sciences (NIGMS) [P41GM103393]
Production of beta-lactamases of one of four molecular classes (A, B, C and D) is the major mechanism of bacterial resistance to beta-lactams, the largest class of antibiotics, which have saved countless lives since their inception 70 years ago. Although several hundred efficient class D enzymes have been identified in Gram-negative pathogens over the last four decades, none have been reported in Gram-positive bacteria. Here we demonstrate that efficient class D. beta-lactamases capable of hydrolyzing a wide array of beta-lactam substrates are widely disseminated in various species of environmental Gram-positive organisms. Class D enzymes of Gram-positive bacteria have a distinct structural architecture and employ a unique substrate-binding mode that is quite different from that of all currently known class A, C and D. beta-lactamases. These enzymes thus constitute a previously unknown reservoir of novel antibiotic-resistance enzymes.
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