Resistance to beta-lactam antibiotics.
beta-lactams have a long history in the treatment of infectious diseases, though their use has been and continues to be confounded by the development of resistance in target organisms. beta-lactamases, particularly in Gram-negative pathogens, are a major determinant of this resistance, although alterations in the beta-lactam targets, the penicillin-binding proteins (PBPs), are also important, especially in Gram-positive pathogens. Mechanisms for the efflux and/or exclusion of these agents also contribute, though often in conjunction these other two. Approaches for overcoming these resistance mechanisms include the development of novel beta-lactamase-stable beta-lactams, beta-lactamase inhibitors to be employed with existing beta-lactams, beta-lactam compounds that bind strongly to low-affinity PBPs and agents that potentiate the activity of existing beta-lactams against low-affinity PBP-producing organisms.
Poole
K
K
Department of Microbiology and Immunology, Queen's University, K7L 3N6, Kingston, Ontario, Canada. poolek@post.queensu.ca
D000900:Anti-Bacterial Agents / Q000378:metabolism; D001426:Bacterial Proteins / Q000502:physiology; D002352:Carrier Proteins / Q000502:physiology; D018432:Drug Resistance, Multiple; D006602:Hexosyltransferases / Q000502:physiology; D002267:Muramoylpentapeptide Carboxypeptidase / Q000502:physiology; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases / Q000502:physiology; D010539:Permeability; D010957:Plasmids; D018440:beta-Lactam Resistance; D001618:beta-Lactamases / Q000378:metabolism
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D001618:beta-Lactamases