The NaHCO-Responsive Phenotype in Methicillin-Resistant Staphylococcus aureus (MRSA) Is Influenced by Genotype.

Methicillin-resistant Staphylococcus aureus (MRSA) strains are a leading cause of many invasive clinical syndromes, and pose treatment difficulties due to their resistance to most β-lactams on standard laboratory testing. A novel phenotype frequently identified in MRSA strains, termed 'NaHCO-responsiveness', is a property whereby strains are susceptible to many β-lactams in the presence of NaHCO. Specific genotypes, repression of /PBP2a expression and perturbed maturation of PBP2a by NaHCO have all been associated with this phenotype. The aim of this study was to define the relationship between specific genotypes and PBP2a substitutions, on the one hand, with NaHCO-responsiveness . Mutations were made in the ribosomal binding site (RBS -7) and at amino acid position 246 of its coding region in parental strains MW2 (NaHCO-responsive) and C36 (NaHCO- nonresponsive) to generate 'swap' variants, each harboring the other's -RBS/coding region genotypes. Successful swaps were confirmed by both sequencing, as well as predicted swap of penicillin-clavulanate susceptibility phenotypes. MW2 swap variants harboring the nonresponsive genotypes became NaHCO-nonresponsive (resistant to the β-lactam, oxacillin [OXA]), in the presence of NaHCO. Moreover, these swap variants had lost NaHCO-mediated repression of /PBP2a expression. In contrast, C36 swap variants harboring the NaHCO-responsive genotypes remained NaHCO-nonresponsive phenotypically, and still exhibited nonrepressible /PBP2a expression. These data demonstrate that in addition to the genotype, NaHCO-responsiveness may also depend on strain-specific genetic backgrounds.