title: Identification of a novel plasmid-mediated beta-lactamase with chromosomal cephalosporinase characteristics from Klebsiella pneumoniae.
abstract: A clinical isolate of Klebsiella pneumoniae resistant to a wide variety of beta-lactams, including third generation cephalosporins, aztreonam and cephamycins, as well as to beta-lactam/clavulanate and sulbactam combinations was examined. It was found that this resistance was transmissible to Escherichia coli recipients via a small 5.3 MDa plasmid encoding for an unusual beta-lactamase produced in relatively large quantities. The enzyme, designated LAT-1, exhibited a highly basic isoelectric point (pI = 9.4) and its hydrolytic activity resembled closely that of a class-I chromosomal cephalosporinase. In vitro, LAT-1 hydrolysed cephaloridine, cephalothin and cephalexin more rapidly than penicillins. A slow hydrolysis of cefoxitin, ceftibuten, ceftazidime and cefotaxime was also observed. The enzyme was inhibited by low concentrations of aztreonam and cloxacillin but it was virtually unaffected by clavulanate. Under stringent conditions, the LAT-1 encoding plasmid did not hybridize with probes specific for TEM-1 and Enterobacter cloacae AmpC beta-lactamase genes. The plasmid was not self-transferable but was readily mobilized by a conjugative R-plasmid harboured by the same K. pneumoniae strain.
authors.affiliation: Department of Bacteriology, Hellenic Pasteur Institute, Athens, Greece.
authors.forename: L S
authors.initials: LS
authors.lastname: Tzouvelekis
authors.forename: E
authors.initials: E
authors.lastname: Tzelepi
authors.forename: A F
authors.initials: AF
authors.lastname: Mentis
authors.forename: A
authors.initials: A
authors.lastname: Tsakris
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002510:Cephalosporinase / Q000235:genetics / Q000302:isolation & purification; D002876:Chromosomes, Bacterial; D019818:Clavulanic Acid; D002969:Clavulanic Acids / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination / Q000494:pharmacology; D007525:Isoelectric Focusing; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000201:enzymology*; D008826:Microbial Sensitivity Tests; D010405:Penicillinase / Q000235:genetics / Q000302:isolation & purification; D010957:Plasmids; D013407:Sulbactam / Q000494:pharmacology; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000235:genetics / Q000302:isolation & purification*
chemical_list: D000900:Anti-Bacterial Agents; D002969:Clavulanic Acids; D065093:beta-Lactamase Inhibitors; D019818:Clavulanic Acid; D002510:Cephalosporinase; D010405:Penicillinase; D001618:beta-Lactamases; D013407:Sulbactam