Telithromycin activity is reduced by efflux in Streptococcus pyogenes

Rafael Cantón1, Annarita Mazzariol, María-Isabel Morosini

  • 1Servicio de Microbiología, Hospital Universitario Ramón y Cajal, Carretera. de Colmenar, Km 9.1, 28034-Madrid, Spain.

Abstract

Insights

Telithromycin can be pumped out of Streptococcus pyogenes by efflux mechanisms. The mef(A) gene is linked to this telithromycin efflux, impacting antibiotic effectiveness.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Pharmacology

Background:

  • Streptococcus pyogenes is a significant human pathogen.
  • Antibiotic resistance, particularly efflux-mediated resistance, is a growing concern.
  • Telithromycin is a ketolide antibiotic used to treat S. pyogenes infections.

Purpose of the Study:

  • To determine if telithromycin is a substrate for efflux pumps in Streptococcus pyogenes.
  • To investigate the genetic basis of telithromycin resistance in S. pyogenes.

Main Methods:

  • Analysis of telithromycin Minimum Inhibitory Concentrations (MICs) in Italian and Spanish S. pyogenes strains.
  • Investigation of efflux mechanisms using radiolabeled [(3)H]telithromycin.
  • Detection of efflux pump genes, including mef(A) and erm(B).

Main Results:

  • Telithromycin MICs were significantly higher in strains expressing the mef(A) gene (M phenotype) compared to susceptible strains.
  • A distinct telithromycin efflux was observed in mef(A)-positive strains, but not in erm(B)-positive or susceptible strains.
  • An msr-like sequence was identified in strains exhibiting telithromycin efflux.

Conclusions:

  • Telithromycin is actively removed from S. pyogenes by efflux pumps.
  • The mef(A) gene is demonstrably involved in telithromycin efflux.
  • The complexity of S. pyogenes efflux systems suggests potential involvement of other genes in telithromycin resistance.

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