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Title: Class D β-lactamases do exist in Gram-positive bacteria

Production of β-lactamases of one of four molecular classes (A, B, C and D) is the major mechanism of bacterial resistance to β-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 β-lactamases capable of hydrolyzing a wide array of β-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 β-lactamases. In conclusion, these enzymes thus constitute a previously unknown reservoir of novel antibiotic-resistance enzymes.
Authors:
 [1] ;  [1] ;  [1] ;  [1] ;  [1] ;  [2] ;  [1]
  1. Univ. of Notre Dame, IN (United States). Dept. of Chemistry and Biochemistry
  2. SLAC National Accelerator Lab., Menlo Park, CA (United States). Stanford Synchrotron Radiation Lightsource (SSRL)
Publication Date:
Grant/Contract Number:
AC02-76SF00515; P41GM103393
Type:
Accepted Manuscript
Journal Name:
Nature Chemical Biology
Additional Journal Information:
Journal Volume: 12; Journal Issue: 1; Journal ID: ISSN 1552-4450
Publisher:
Nature Publishing Group
Research Org:
SLAC National Accelerator Lab., Menlo Park, CA (United States)
Sponsoring Org:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22); USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23); National Institutes of Health (NIH)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; 59 BASIC BIOLOGICAL SCIENCES; Bacteria; Enzymes; X-ray crystallography
OSTI Identifier:
1257221

Toth, Marta, Antunes, Nuno Tiago, Stewart, Nichole K., Frase, Hilary, Bhattacharya, Monolekha, Smith, Clyde A., and Vakulenko, Sergei B.. Class D β-lactamases do exist in Gram-positive bacteria. United States: N. p., Web. doi:10.1038/nchembio.1950.
Toth, Marta, Antunes, Nuno Tiago, Stewart, Nichole K., Frase, Hilary, Bhattacharya, Monolekha, Smith, Clyde A., & Vakulenko, Sergei B.. Class D β-lactamases do exist in Gram-positive bacteria. United States. doi:10.1038/nchembio.1950.
Toth, Marta, Antunes, Nuno Tiago, Stewart, Nichole K., Frase, Hilary, Bhattacharya, Monolekha, Smith, Clyde A., and Vakulenko, Sergei B.. 2015. "Class D β-lactamases do exist in Gram-positive bacteria". United States. doi:10.1038/nchembio.1950. https://www.osti.gov/servlets/purl/1257221.
@article{osti_1257221,
title = {Class D β-lactamases do exist in Gram-positive bacteria},
author = {Toth, Marta and Antunes, Nuno Tiago and Stewart, Nichole K. and Frase, Hilary and Bhattacharya, Monolekha and Smith, Clyde A. and Vakulenko, Sergei B.},
abstractNote = {Production of β-lactamases of one of four molecular classes (A, B, C and D) is the major mechanism of bacterial resistance to β-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 β-lactamases capable of hydrolyzing a wide array of β-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 β-lactamases. In conclusion, these enzymes thus constitute a previously unknown reservoir of novel antibiotic-resistance enzymes.},
doi = {10.1038/nchembio.1950},
journal = {Nature Chemical Biology},
number = 1,
volume = 12,
place = {United States},
year = {2015},
month = {11}
}