The Carboxyl Terminus of Peptidoglycan Stem Peptides Is a Determinant for Methicillin Resistance in Staphylococcus aureus

A mecA-containing Staphylococcus aureus strain was grown in the presence of high concentrations of d-serine, d-threonine, and d-phenylalanine. These growth conditions resulted in the replacement of the carboxyl-terminal (fifth) d-alanine residue of peptidoglycan stem peptides with the d-amino acid present in the growth medium and a reduced ability to grow in the presence of methicillin. The most dramatic effect was seen with d-serine. With 32 mM d-serine, strains that had been able to grow in the presence of 800 μg of methicillin per ml were only able to grow in the presence of less than 50 μg/ml. The results also suggest that in S. aureus vancomycin resistance mediated through the incorporation of precursors not terminating in d-alanyl-d-alanine would be mutually exclusive with expression of mecA-mediated methicillin resistance.