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Molecular evolution of ubiquitous β‐lactamases towards extended‐spectrum enzymes active against newer β‐lactam antibiotics
Author(s) -
Collatz E.,
Labia R.,
Gutmann L.
Publication year - 1990
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.1990.tb00537.x
Subject(s) - biology , plasmid , enzyme , mutant , cephalosporin , point mutation , active site , antibiotics , bacteria , mutation , genetics , gene , biochemistry , microbiology and biotechnology , stereochemistry , chemistry
Summary Production of β‐lactamases, and of the plasmid‐encoded TEM‐and SHV‐type enzymes in particular, is the most common mechanism of resistance against β‐lactam antibiotics in Gram‐negative bacteria. The two ubiquitous types of enzyme have a large spectrum of activity and preferentially hydrolyse the penicillins as well as some first‐and second‐generation cephalosporins. Recently, point mutations in the corresponding genes have been observed, apparently selected for, in the clinical setting, by originally ‘β‐lactamase‐stable’ third‐generation cephalosporins or by mono‐bactams, which fall into the substrate range of the mutant or ‘extended‐spectrum’β‐lactamases. The point mutations are clustered in three areas, each adjacent to one of the seven evolutionarily conserved boxes described by Joris et al. (1988). The substituted amino acids at positions 102 (adjacent to the α‐3 helix), 162 (adjacent to the α‐7 helix) and 235,236 and 237 (on the β‐3 strand) are located in close proximity to the active‐site cavity and are thought to open up novel enzyme‐substrate interactions, involving, in particular, the oxyimino moieties of the newer β‐lactam compounds.