title: Selection of naturally occurring extended-spectrum TEM beta-lactamase variants by fluctuating beta-lactam pressure.
abstract: Despite the large number of in vitro mutations that increase resistance to extended-spectrum cephalosporins in TEM-type beta-lactamases, only a small number occur in naturally occurring enzymes. In nature, and particularly in the hospital, bacteria that contain beta-lactamases encounter simultaneous or consecutive selective pressure with different beta-lactam molecules. All variants obtained by submitting an Escherichia coli strain that contains a bla(TEM-1) gene to fluctuating challenge with both ceftazidime and amoxicillin contained only mutations previously detected in naturally occurring beta-lactamases. Nevertheless, some variants obtained by ceftazidime challenge alone contained mutations never detected in naturally occurring TEM beta-lactamases, suggesting that extended-spectrum TEM variants in hospital isolates result from fluctuating selective pressure with several beta-lactams rather than selection with a single antibiotic.
authors.affiliation: Servicio de Microbiología, Hospital Ramón y Cajal, Madrid 28034, Spain. jblazquez@hrc.insalud.es
authors.forename: J
authors.initials: J
authors.lastname: Blazquez
authors.forename: M I
authors.initials: MI
authors.lastname: Morosini
authors.forename: M C
authors.initials: MC
authors.lastname: Negri
authors.forename: F
authors.initials: F
authors.lastname: Baquero
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D017354:Point Mutation; D012641:Selection, Genetic; D018440:beta-Lactam Resistance / Q000235:genetics*; D001618:beta-Lactamases / Q000235:genetics* / Q000378:metabolism; D047090:beta-Lactams
chemical_list: D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D001618:beta-Lactamases; C034413:beta-lactamase TEM-1