title: Properties of plasmids responsible for production of extended-spectrum beta-lactamases.
abstract: The extended-spectrum beta-lactamases are believed to arise by mutations which alter the configuration around the active site of TEM- and SHV-type enzymes so as to increase their efficiency with otherwise nonhydrolyzable cephalosporins and monobactams. This hypothesis predicts that the genes for these new enzymes should be found on the same wide variety of plasmids that encode TEM-1, TEM-2, and SHV-1 beta-lactamases and that at least some of them should be mediated by transposons. Fifteen plasmids, each encoding an extended-spectrum beta-lactamase, were examined. Unlike the average TEM plasmid, all were large, ranging in size from 80 to 300 kb. All determined resistance to multiple antimicrobial agents, ranging from 5 to 11, and some conferred resistance to heavy metals and UV radiation as well. The plasmids belonged to a limited number of incompatibility (Inc) groups, including IncC, IncFI, IncHI2, and IncM. Because most of the mutations giving rise to extended-spectrum activity are G.C----A.T transitions and some of the mutant genes have as many as four base substitutions, a plasmid-determined mutator gene was searched for, but no such property was found. Several techniques were used to detect transposition of the extended-spectrum beta-lactamase genes, but a mobile genetic element could not be demonstrated even though eight of the plasmids hybridized with a DNA probe derived from the tnpR gene of Tn3. The genesis of extended-spectrum beta-lactamases may not be as simple as has been supposed.
authors.affiliation: Massachusetts General Hospital, Boston 02114.
authors.forename: G A
authors.initials: GA
authors.lastname: Jacoby
authors.forename: L
authors.initials: L
authors.lastname: Sutton
mesh_terms: D004251:DNA Transposable Elements / Q000502:physiology; D009154:Mutation; D010957:Plasmids / Q000235:genetics*; D001618:beta-Lactamases / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D004251:DNA Transposable Elements; D001618:beta-Lactamases