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Staphylococcus aureus adaptation to vancomycin influences phage susceptibility

Jack Å H Abrahamsson1, Esther Lehmann1, Anaëlle Fait2

  • 1Department of Veterinary and Animal Sciences, Section for Bacteria and Viruses, University of Copenhagen, Frederiksberg, 1870, Copenhagen, Denmark.

Research in Microbiology
|September 28, 2025
PubMed

Insights

Bacterial phages show altered efficacy against Staphylococcus aureus strains with vancomycin-intermediate susceptibility (VISA). VISA development can change phage susceptibility, impacting phage therapy effectiveness and necessitating careful consideration of antibiotic-drug interactions.

Area of Science:

  • Microbiology
  • Bacteriology
  • Virology

Background:

  • Bacterial phages are promising therapeutics against antibiotic-resistant pathogens.
  • Staphylococcus aureus strains, particularly methicillin-resistant (MRSA) and vancomycin-intermediate susceptible (VISA) strains, commonly exhibit resistance to antibiotics.
  • Wall teichoic acid (WTA) glycopolymers on the bacterial cell wall serve as primary phage receptors.

Purpose of the Study:

  • To investigate how mutations leading to vancomycin-intermediate susceptibility affect phage susceptibility in Staphylococcus aureus.
  • To evaluate the impact of antibiotic-driven physiological changes on phage therapy efficacy.
  • To explore the relationship between WTA glycosylation and phage resistance.

Main Methods:

  • Analysis of phage susceptibility in clinical and laboratory-evolved VISA strains of Staphylococcus aureus.
  • Infection modeling using therapeutically relevant myoviruses (ΦIPLA-RODI, Stab20, Stab21, ΦK).
  • Assessment of WTA glycosylation patterns and phage therapy efficacy in a Galleria mellonella infection model.

Main Results:

  • VISA development in Staphylococcus aureus led to variable changes in phage susceptibility, with some strains becoming more resistant and others more susceptible.
  • Laboratory-evolved VISA strains showed resistance to certain phages, while some became susceptible to previously resistant phages.
  • Altered WTA glycosylation correlated with changes in phage susceptibility, and resistance compromised phage therapy effectiveness in vivo.

Conclusions:

  • Antibiotic-induced alterations in bacterial physiology, specifically WTA glycosylation, significantly impact phage susceptibility in Staphylococcus aureus.
  • Understanding these changes is crucial for developing effective phage-based therapies, especially when used in combination with antibiotics.
  • Future phage therapy strategies must account for antibiotic-driven bacterial adaptations to ensure successful treatment outcomes.
Keywords:
Galleria mellonellaPhage therapyStaphylococcus aureusVISAVirulenceWTA

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