Mutations in folP associated with elevated sulfonamide MICs for Neisseria meningitidis clinical isolates from five

K R Fiebelkorn1, S A Crawford, J H Jorgensen

  • 1Department of Pathology, University of Texas Health Science Center, 7703 Floyd Curl Dr., MC 7750, San Antonio, TX 78229-3750, USA. fiebelkorn@uthscsa.edu

Insights

Sulfonamide resistance in meningococci is linked to mutations in the folP gene. The C682A mutation strongly predicts elevated sulfonamide MICs, offering a high-throughput screening method for Neisseria meningitidis.

Area of Science:

  • Microbiology
  • Genetics
  • Antimicrobial Resistance

Background:

  • Sulfonamide resistance in Neisseria meningitidis is primarily associated with mutations in the folP gene, encoding dihydropteroate synthase.
  • Previously identified mutations include amino acid substitutions and insertions, but a recent mutation at nucleotide 682 (C682A) has emerged.

Purpose of the Study:

  • To investigate the prevalence and impact of the C682A mutation on sulfonamide resistance in geographically diverse clinical isolates of Neisseria meningitidis.
  • To evaluate the C682A mutation as a potential marker for predicting elevated sulfonamide minimum inhibitory concentrations (MICs).

Main Methods:

  • Determination of sulfisoxazole MICs for 424 clinical isolates of Neisseria meningitidis.
  • Real-time PCR assay to detect the C682A mutation in a subset of isolates.
  • folP gene sequencing for a selected group of isolates with varying MICs.

Main Results:

  • All isolates with a sulfisoxazole MIC of ≥8 μg/ml possessed the C682A mutation, while 34 of 35 isolates with a MIC of ≤2 μg/ml lacked it.
  • Among sequenced isolates with MICs ≥4 μg/ml, 15 of 16 had previously described mutations, and all 16 also possessed the C682A mutation.
  • The C682A mutation was consistently associated with elevated sulfonamide MICs across diverse meningococcal isolates.

Conclusions:

  • The C682A mutation is a significant predictor of elevated sulfonamide MICs in Neisseria meningitidis.
  • Detection of the C682A mutation offers a simple, high-throughput screening method for identifying sulfonamide-resistant meningococci, valuable for public health and epidemiology.

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