A S₁₈₀F substitution in D-alanine aminotransferase confers resistance to β-chloro-D-alanine in Staphylococcus aureus.

ABSTRACT: β-lactam antibiotics that target the synthesis of bacterial cell wall peptidoglycan (PG) remain a cornerstone of antimicrobial chemotherapy. The activity of β-lactams against methicillin-resistant Staphylococcus aureus (MRSA) can be enhanced by the alanine analog d-cycloserine (DCS), which blocks alanine racemase (Alr1) and d-alanine ligase (Ddl) and interferes with the supply of d-alanine for PG synthesis. Here, we report that another alanine analogue antibiotic, β-chloro-d-alanine (BCDA), also interferes with the d-alanine pathway by targeting d-alanine aminotransferase (Dat), which converts pyruvate to d-alanine. A Dat S₁₈₀F substitution, identified in a BCDA resistant MRSA mutant, resulted in reduced transaminase activity. X-ray crystallographic analysis of S. aureus Dat all

SUBMITTER: Roy R 

PROVIDER: S-EPMC12723384 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature