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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.
The Journal of Antimicrobial Chemotherapy
|February 12, 2005
Summary
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.