Emergence of clinical isolates of Escherichia coli producing TEM-1 derivatives or an OXA-1 beta-lactamase conferring resistance to beta-lactamase inhibitors.
Sixteen Escherichia coli clinical isolates which were resistant to ampicillin and amoxicillin-clavulanate but susceptible to cephalothin were studied. Eight strains showed the presence of a beta-lactamase which comigrates with reference OXA-1 enzyme. The eight other strains produced different TEM-1 derivatives which had in common a higher Km for penicillins and a higher 50% inhibitory concentration for the beta-lactamase inhibitors. By oligotyping and sequencing of PCR products, it was shown that Ser (AGC) (TEM-30; also called TRI-1) in three strains and Cys (TGC) (TEM-31; also called TRI-2) in one strain were substituted for Arg-241 (CGC), that Leu (CTG) (TEM-33) and Val (GTG) (TEM-34) in one strain each were substituted for Met-67 (ATG), and that in other mutants the two latter substitutions occurred together with the substitution of Asp (GAT) (TEM-35 and TEM-36) for Asn-272 (AAT). Therefore, different sets of amino acid substitutions of TEM-1 can be found in clinical isolates and lead to resistance to beta-lactamase inhibitors.
Zhou
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Laboratoire de Microbiologie Médicale, Université Paris VI, France.
Bordon
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F
Sirot
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Kitzis
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MD
Gutmann
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L
D000658:Amoxicillin / Q000494:pharmacology; D001483:Base Sequence; D002512:Cephalothin / Q000494:pharmacology; D019818:Clavulanic Acid; D002969:Clavulanic Acids / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D004927:Escherichia coli Infections / Q000382:microbiology*; D006801:Humans; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000096:biosynthesis*
D002969:Clavulanic Acids; D065093:beta-Lactamase Inhibitors; D019818:Clavulanic Acid; D000658:Amoxicillin; C039404:beta-lactamase OXA-2; D001618:beta-Lactamases; C034413:beta-lactamase TEM-1; D002512:Cephalothin