Open AccessCTX-M-93, a CTX-M Variant Lacking Penicillin Hydrolytic Activity
Author(s) -
Laura Djamdjian,
Thierry Naas,
Didier Tandé,
Gaëlle Cuzon,
Catherine Hanrotel-Saliou,
Patrice Nordmann
Publication year - 2011
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.01656-10
Subject(s) - cefotaxime , ceftazidime , cephalosporin , microbiology and biotechnology , penicillin , clavulanic acid , escherichia coli , beta lactamase , ticarcillin , biology , multilocus sequence typing , plasmid , antibiotics , gene , genotype , bacteria , amoxicillin , biochemistry , genetics , pseudomonas aeruginosa
Extended-spectrum β-lactamases (ESBLs) of the CTX-M type are increasingly being reported worldwide, with more than 90 known variants. ClinicalEscherichia coli isolate Bre-1 was isolated in 2009 and displayed an unusual ESBL phenotype, made of a synergy image between expanded cephalosporins and clavulanic acid discs and susceptibility to penicillins.E. coli Bre-1 harbored a novel CTX-M-encoding gene, designatedbla CTX-M-93 . CTX-M-93 differed from CTX-M-27 by only a single L169Q substitution. Compared to CTX-M-27, CTX-M-93 conferred higher MICs of ceftazidime forE. coli (MIC of 8 versus 1.5 μg/ml) and decreased MICs of other expanded-cephalosporins (MIC of cefotaxime of 1 versus 32 μg/ml) and penicillins (MIC of ticarcillin of 0.5 versus >256 μg/ml). A comparison of enzymatic properties revealed that the L169Q substitution led to a decreasedKm for ceftazidime (25.5 versus 330 μM) but decreased hydrolytic activity against good substrates, such as cefotaxime (k cat of 0.6 versus 113 s−1 ), probably owing to the alteration of the omega loop positioning during the catalytic process. Thebla CTX-M-93 gene was surrounded by the ISEcp1 and IS903 elements and inserted onto a 150-kb non-self-transferrable IncF-type plasmid.E. coli Bre-1 belongs to phylogroup D and is of multilocus sequence type (MLST) 624, a sequence type found only in rare Spanish CTX-M-14-producingE. coli isolates. We have characterized a novel CTX-M variant, CTX-M-93, lacking significant penicillin hydrolysis but with increased ceftazidime hydrolysis.