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Updated: Aug 15, 2026

High Throughput, Real-time, Dual-readout Testing of Intracellular Antimicrobial Activity and Eukaryotic Cell Cytotoxicity
Published on: November 16, 2016
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.
Objectives:
To investigate whether telithromycin is a substrate for efflux pumps in Streptococcus pyogenes.
Methods:
The distribution of telithromycin MICs was analysed for two distinct collections of Italian (n=486) and Spanish (n=210) S. pyogenes strains. The effect of an efflux mechanism was investigated using [(3)H]telithromycin.
Results:
Telithromycin MIC ranges were < or = 0.004-0.06 mg/L (MIC(50) and MIC(90), 0.01 mg/L) in erythromycin-susceptible strains (lacking both mef and erm genes) and 0.01-1 mg/L (MIC(50) and MIC(90), 0.5 mg/L) in strains endowed with the M phenotype and expressing the mef(A) gene. A distinct telithromycin efflux was detected in the strains expressing the mef(A) gene, but not in those expressing the erm(B) gene, nor in the susceptible strains lacking mef(A) or erm genes. Efflux reversibility by addition of an inhibiting compound (sodium arsenate) was demonstrated. An msr-like sequence was also found in all strains effluxing telithromycin, but not in the others.
Conclusions:
This study shows that telithromycin can be removed from S. pyogenes by efflux. That the efflux is related to the presence of the mef(A) gene is demonstrated, but-owing to the increasingly evident complexity of S. pyogenes efflux systems-the possibility that other genes may contribute to the efflux cannot be excluded.
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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