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Published on: March 2, 2020
Macrolide resistance mechanisms in Gram-positive cocci
1Department of Microbiology and Genetics, University Medical Centre, 1 Rue Michel Servet, CH-1211, Geneva, Switzerland. pechere@cmu.unige.ch
Abstract:
Two principal mechanisms of resistance to macrolides have been identified in Gram-positive bacteria. Erythromycin-resistant methylase is encoded by erm genes. Resultant structural changes to rRNA prevent macrolide binding and allow synthesis of bacterial proteins to continue. Presence of the erm gene results in high-level resistance. Modification of the mechanism whereby antibiotics are eliminated from the bacteria also brings about resistance. Bacteria carrying the gene encoding macrolide efflux (i.e. the mefE gene) display relatively low-level resistance. Azithromycin, because of its ability to achieve concentrations at sites of infections, is capable of eradicating mefE-carrying strains. Other resistance mechanisms, involving stimulation of enzymatic degradation, appear not to be clinically significant.
Insights
Two main antibiotic resistance mechanisms exist in Gram-positive bacteria: erm genes causing high-level resistance and mefE genes enabling low-level macrolide efflux. Azithromycin effectively targets strains with mefE genes.
Area of Science:
- Microbiology
- Molecular Biology
- Pharmacology
Background:
- Gram-positive bacteria exhibit resistance to macrolide antibiotics through identified genetic mechanisms.
- Two primary resistance pathways involve ribosomal RNA modification and active antibiotic efflux.
Purpose of the Study:
- To elucidate the principal mechanisms of macrolide resistance in Gram-positive bacteria.
- To differentiate the clinical significance and resistance levels associated with specific macrolide resistance genes.
Main Methods:
- Analysis of genetic determinants of macrolide resistance, specifically erm and mefE genes.
- Evaluation of bacterial protein synthesis inhibition and antibiotic efflux mechanisms.
- Assessment of azithromycin efficacy against bacteria harboring mefE genes.
Main Results:
- The erm gene confers high-level macrolide resistance by altering ribosomal RNA structure, preventing antibiotic binding.
- The mefE gene mediates low-level macrolide resistance through an efflux mechanism.
- Azithromycin demonstrated efficacy in eradicating mefE-carrying bacterial strains due to its concentration at infection sites.
Conclusions:
- Erm-mediated ribosomal modification and mefE-mediated efflux are key macrolide resistance mechanisms in Gram-positive bacteria.
- Resistance levels vary significantly between these two mechanisms.
- Azithromycin holds therapeutic potential against specific macrolide-resistant bacterial infections.
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