Impact of Bicarbonate on PBP2a Production, Maturation, and Functionality in Methicillin-Resistant Staphylococcus aureus

Certain methicillin-resistant Staphylococcus aureus (MRSA) strains exhibit β-lactam susceptibility in vitro, ex vivo, and in vivo in the presence of NaHCO(3) (NaHCO(3)-responsive MRSA). Here, we investigate the impact of NaHCO(3) on factors required for PBP2a functionality. Prototype NaHCO(3)-responsive and -nonresponsive MRSA strains (as defined in vitro) were assessed for the impact of NaHCO(3) on the expression of genes involved in PBP2a production-maturation pathways (mecA, blaZ, pbp4, vraSR, prsA, sigB, and floA), membrane PBP2a and PrsA protein content, and membrane carotenoid content. Following NaHCO(3) exposure in NaHCO(3)-responsive (versus nonresponsive) MRSA, there was significantly reduced expression of (i) mecA and blaZ, (ii) the vraSR-prsA gene axis, and (iii) pbp4. Carotenoid production was reduced while floA expression was increased by NaHCO(3) exposure in all MRSA strains. This work underscores the distinct regulatory impact of NaHCO(3) on a cadre of genes encoding factors required for the maintenance of the MRSA phenotype through PBP2a functionality and maturation.