title: Solving staphylococcal resistance to beta-lactams.
abstract: Class resistance to beta-lactam antibiotics in Gram-positive bacteria is mediated by structural changes in transpeptidase penicillin-binding proteins. These structural changes render a complex series of interactions between antibiotic and protein that are energetically unfavorable, such that the active site is inactivated not at all or too slowly to prevent cell-wall synthesis and bacterial growth. Determination of the crystal structure of the low-affinity penicillin-binding protein PBP2a, which mediates beta-lactam antibiotic resistance in staphylococci, has identified the molecular structures and interactions that are responsible for resistance. This information could be useful for designing beta-lactams to overcome these structural impediments, as well as resistance.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, San Francisco General Hospital, Box 0811, 3rd and Parnassus Avenues, San Francisco, CA 94110, USA. chipc@itsa.ucsf.edu
authors.forename: Henry F
authors.initials: HF
authors.lastname: Chambers
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D016106:Methicillin Resistance / Q000502:physiology*; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D013210:Staphylococcus / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship; D018440:beta-Lactam Resistance / Q000502:physiology; D047090:beta-Lactams
chemical_list: D000900:Anti-Bacterial Agents; D047090:beta-Lactams