The Removal Of D-Alanine From The Cell Wall Teichoic Acids Of Staphylococcus Aureus By The Fmta Protein Drives Strain-Specific Viability Alterations Under Environmental Stress Conditions

Abstract

Antibiotic resistance of highly infectious Staphylococcus aureus makes eliminating this microorganism increasingly difficult, contributing to hospitalizations and severe infections worldwide. Wall teichoic acids (WTAs), linked to the bacterial cell wall, play key roles in resistance, cell lysis, and survival. WTAs are modified by the addition of D-alanine (D-Ala), which helps control bacterial surface charge and antibiotic resistance. S. aureus naturally cleaves D-Ala using the enzyme FmtA. We investigated whether purified FmtA could influence bacterial growth and survival by removing D-Ala from WTAs in vivo under favourable or unfavourable environments. Our findings confirmed that FmtA removes D-Ala from S. aureus and other Gram-positive bacteria. While S. aureus viability remained stable under favourable conditions, strain-specific responses emerged under variable stress. Notably, methicillin-resistant strains became more sensitive to oxacillin when exposed to FmtA. These results suggest that targeting WTA modifications could be a strategy to alter S. aureus viability under specific stress-inducing conditions.