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

Certain methicillin-resistant Staphylococcus aureus (MRSA) strains exhibit β-lactam-susceptibility in vitro, ex vivo and in vivo in the presence of NaHCO₃ (NaHCO₃-responsive MRSA). Herein, we investigate the impact of NaHCO₃ on factors required for PBP2a functionality. Prototype NaHCO₃-responsive and -nonresponsive MRSA strains (as defined in vitro) were assessed for the impact of NaHCO₃ on: 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 NaHCO₃ exposure in NaHCO₃-responsive (vs - 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 NaHCO₃ exposure in all MRSA strains. This work underscores the distinct regulatory impact of NaHCO₃ on a cadre of genes encoding factors required for maintenance of the MRSA phenotype through PBP2a functionality and maturation.