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Antibiotic resistance is a major public health concern that arises when bacteria evolve mechanisms to withstand the effects of antibiotic treatments. This resistance can be intrinsic, acquired through genetic mutations, or transferred between bacteria via horizontal gene transfer. The development of antibiotic resistance poses significant challenges in treating bacterial infections and necessitates ongoing research to develop new therapeutic strategies.Intrinsic resistance occurs when bacterial...
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The effectiveness of antimicrobial agents depends on various factors influencing their ability to eliminate microbial populations. Larger microbial populations require more time for complete eradication, emphasizing the importance of population size analysis when evaluating antimicrobial efficacy.Microbial resistance to antimicrobial agents varies significantly. Highly resilient microorganisms include endospores, gram-negative bacteria, and non-enveloped viruses, while prions are exceptionally...
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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.