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CTX-M-93, a CTX-M variant lacking penicillin hydrolytic activity
Laura Djamdjian1, Thierry Naas, Didier Tandé
1Service de Bactériologie-Virologie, INSERM U914, Emerging Resistance to Antibiotics, Hôpital de Bicêtre, Assistance Publique-Hôpitaux de Paris, Faculté de Médecine Paris-Sud, Le Kremlin-Bicêtre, France.
Antimicrobial Agents and Chemotherapy
|February 24, 2011
Summary
A novel extended-spectrum β-lactamase (ESBL), CTX-M-93, was identified in clinical Escherichia coli. This variant shows increased ceftazidime hydrolysis and reduced penicillin activity, offering new insights into ESBL evolution.
Area of Science:
- Microbiology
- Molecular Biology
- Biochemistry
Background:
- Extended-spectrum β-lactamases (ESBLs) are a growing global health concern, with over 90 CTX-M variants identified.
- Clinical Escherichia coli isolate Bre-1 exhibited an unusual ESBL phenotype, including synergy between cephalosporins and clavulanic acid, alongside penicillin susceptibility.
Purpose of the Study:
- To characterize a novel CTX-M-type ESBL gene, designated blaCTX-M-93, identified in the clinical E. coli Bre-1 isolate.
- To investigate the impact of a specific amino acid substitution (L169Q) on the enzymatic properties and antimicrobial resistance profile of the novel ESBL.
Main Methods:
- Identification and sequencing of the novel blaCTX-M-93 gene in E. coli Bre-1.
- Determination of minimum inhibitory concentrations (MICs) for various β-lactam antibiotics against E. coli expressing CTX-M-93.
- Enzymatic characterization of CTX-M-93, including kinetic parameters (Km, kcat) for different substrates.
- Analysis of the genetic environment and plasmid context of the blaCTX-M-93 gene.
Main Results:
- The novel CTX-M-93 variant, differing from CTX-M-27 by a single L169Q substitution, was identified.
- CTX-M-93 conferred significantly higher ceftazidime MICs (8 μg/ml) but lower cefotaxime (1 μg/ml) and ticarcillin (>256 μg/ml) MICs compared to CTX-M-27.
- Enzymatic assays showed CTX-M-93 has decreased Km for ceftazidime and reduced hydrolytic activity against cefotaxime, attributed to omega loop alterations.
- The blaCTX-M-93 gene was located on a 150-kb IncF plasmid, flanked by ISEcp1 and IS903 elements.
Conclusions:
- The novel CTX-M-93 variant exhibits a unique resistance profile with enhanced ceftazidime hydrolysis and diminished penicillin activity.
- The L169Q substitution significantly alters the enzymatic properties of CTX-M-93, impacting its substrate specificity and catalytic efficiency.
- The characterization of CTX-M-93 provides valuable insights into the ongoing evolution of ESBL-producing bacteria and their resistance mechanisms.
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