Staphylococcus aureus adaptation to vancomycin influences phage susceptibility

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.