Open AccessClass D β-lactamases do exist in Gram-positive bacteria
Author(s) -
Márta Tóth,
Nuno T. Antunes,
Nichole K. Stewart,
Hilary Frase,
Monolekha Bhattacharya,
Clyde A. Smith,
Sergei B. Vakulenko
Publication year - 2015
Publication title -
nature chemical biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.412
H-Index - 216
eISSN - 1552-4469
pISSN - 1552-4450
DOI - 10.1038/nchembio.1950
Subject(s) - bacteria , gram , enzyme , biology , gram negative bacteria , microbiology and biotechnology , antibiotics , gram positive bacteria , computational biology , biochemistry , genetics , escherichia coli , gene
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. These enzymes thus constitute a previously unknown reservoir of novel antibiotic-resistance enzymes.