OXA-35 is an OXA-10-related beta-lactamase from Pseudomonas aeruginosa

D Aubert1, L Poirel, A B Ali

  • 1Service de Bactériologie-Virologie, Hôpital de Bicêtre, Assistance Publique/Hôpitaux de Paris, Faculté de Médecine Paris-Sud, 94275 Le Kremlin-Bicêtre, Paris, France.

Insights

A new beta-lactamase, OXA-35, was identified in Pseudomonas aeruginosa PA35. This enzyme confers resistance to certain penicillins and may be a progenitor of OXA-13-like extended-spectrum beta-lactamases.

Area of Science:

  • Microbiology
  • Biochemistry
  • Genetics

Background:

  • Pseudomonas aeruginosa is an opportunistic pathogen known for its intrinsic and acquired antibiotic resistance.
  • Beta-lactamases are key enzymes responsible for the hydrolysis of beta-lactam antibiotics, contributing significantly to bacterial resistance.
  • The emergence of novel beta-lactamase variants necessitates continuous surveillance and characterization to understand resistance mechanisms.

Purpose of the Study:

  • To identify and characterize the beta-lactamase responsible for the observed antibiotic resistance in Pseudomonas aeruginosa clinical isolate PA35.
  • To determine the genetic basis and substrate hydrolysis profile of the novel beta-lactamase variant.

Main Methods:

  • Antibiotic susceptibility testing of Pseudomonas aeruginosa PA35.
  • Cloning and sequencing of the beta-lactamase gene from the clinical isolate.
  • Biochemical characterization of the purified beta-lactamase to determine its substrate hydrolysis profile.

Main Results:

  • Pseudomonas aeruginosa PA35 exhibited resistance to amino- and ureido-penicillins and intermediate susceptibility to cefsulodin, cefepime, and aztreonam.
  • A novel beta-lactamase, designated OXA-35, was identified and found to share 96% amino acid identity with OXA-10.
  • OXA-35 demonstrated a restricted substrate hydrolysis profile with enhanced hydrolysis of amoxicillin and cloxacillin compared to OXA-10.

Conclusions:

  • The novel beta-lactamase OXA-35 contributes to the resistance phenotype of Pseudomonas aeruginosa PA35.
  • OXA-35 represents a distinct variant within the OXA beta-lactamase family, potentially serving as a progenitor for OXA-13-like extended-spectrum beta-lactamases.

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