High-level chloramphenicol resistance in Neisseria meningitidis

M Galimand1, G Gerbaud, M Guibourdenche

  • 1National Reference Center for Antibiotics, Institut Pasteur, Paris, France.

Abstract

Insights

Chloramphenicol resistance in Neisseria meningitidis is a growing concern. This resistance, caused by the catP gene on a transposon, threatens standard meningitis treatment in developing nations.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Genetics

Background:

  • Neisseria meningitidis is typically susceptible to penicillin, cephalosporins, and chloramphenicol.
  • However, chloramphenicol-resistant strains were identified in Vietnam and France between 1987 and 1996.

Purpose of the Study:

  • To characterize chloramphenicol-resistant Neisseria meningitidis isolates.
  • To identify the genetic basis and origin of chloramphenicol resistance.

Main Methods:

  • Minimal inhibitory concentration determination for chloramphenicol.
  • Serotyping, subtyping, pulsed-field gel electrophoresis, and multilocus enzyme electrophoresis.
  • DNA analysis including hybridization, PCR, and sequencing to identify resistance genes and their origins.

Main Results:

  • All 12 isolates exhibited high-level chloramphenicol resistance (MIC ≥64 mg/L) and produced chloramphenicol acetyltransferase.
  • Strains belonged to serogroup B but showed significant diversity; 10 were untypeable by monoclonal antibodies.
  • The resistance gene and flanking regions matched an internal portion of transposon Tn4451, carrying the catP gene from Clostridium perfringens, located at the same genomic site in resistant isolates.

Conclusions:

  • High-level chloramphenicol resistance in N. meningitidis is concerning due to its use as standard therapy for meningococcal meningitis in developing countries.
  • Resistance is attributed to the catP gene on a truncated, immobile transposon.
  • Genetic material transformation between N. meningitidis strains likely facilitated gene dissemination.

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