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Updated: Sep 27, 2025
Nanomechanics of Drug-target Interactions and Antibacterial Resistance Detection
Published on: October 25, 2013
Collateral sensitivity to pleuromutilins in vancomycin-resistant Enterococcus faecium
Qian Li1, Shang Chen1, Kui Zhu2,3
1National Center for Veterinary Drug Safety Evaluation, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China.
Abstract:
The acquisition of resistance to one antibiotic sometimes leads to collateral sensitivity to a second antibiotic. Here, we show that vancomycin resistance in Enterococcus faecium is associated with a remarkable increase in susceptibility to pleuromutilin antibiotics (such as lefamulin), which target the bacterial ribosome. The trade-off between vancomycin and pleuromutilins is mediated by epistasis between the van gene cluster and msrC, encoding an ABC-F protein that protects bacterial ribosomes from antibiotic targeting. In mouse models of vancomycin-resistant E. faecium colonization and septicemia, pleuromutilin treatment reduces colonization and improves survival more effectively than standard therapy (linezolid). Our findings suggest that pleuromutilins may be useful for the treatment of vancomycin-resistant E. faecium infections.
Insights
Vancomycin resistance in Enterococcus faecium surprisingly increases susceptibility to pleuromutilin antibiotics. This finding suggests pleuromutilins as a potential treatment for infections caused by vancomycin-resistant bacteria.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Antibiotic resistance is a growing global health threat.
- Cross-resistance and collateral sensitivity are key phenomena in antibiotic resistance.
- Enterococcus faecium is a common cause of hospital-acquired infections, often resistant to vancomycin.
Purpose of the Study:
- To investigate the phenomenon of collateral sensitivity in vancomycin-resistant Enterococcus faecium.
- To explore the potential of pleuromutilin antibiotics as an alternative treatment for vancomycin-resistant Enterococcus faecium infections.
Main Methods:
- Investigated the susceptibility of vancomycin-resistant Enterococcus faecium to pleuromutilin antibiotics.
- Analyzed the genetic basis of the observed collateral sensitivity, focusing on epistasis between the van gene cluster and msrC.
- Evaluated the efficacy of pleuromutilin treatment in mouse models of vancomycin-resistant Enterococcus faecium colonization and septicemia.
Main Results:
- Vancomycin resistance in Enterococcus faecium was associated with increased susceptibility to pleuromutilins.
- Epistasis between the van gene cluster and msrC was identified as the mechanism mediating this trade-off.
- Pleuromutilin treatment demonstrated superior efficacy in reducing colonization and improving survival in mouse models compared to linezolid.
Conclusions:
- Pleuromutilin antibiotics exhibit collateral sensitivity in vancomycin-resistant Enterococcus faecium.
- The genetic interaction between van genes and msrC underlies this phenomenon.
- Pleuromutilins represent a promising therapeutic option for treating vancomycin-resistant Enterococcus faecium infections.
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