Physiological role of bicarbonate in microbes: A double-edged sword?

HCO₃^- is involved in pH homoeostasis and plays a multifaceted role in human health. HCO₃^- has been recognized for its antimicrobial properties and is pivotal in bacterial antibiotic susceptibility. Notably, the interconversion between CO₂ and HCO₃^-, facilitated by the enzyme carbonic anhydrase (CA), is crucial in tissues infected by pathogens. Studies have highlighted the antimicrobial potency of CA inhibitors, emphasizing the importance of this enzyme in this area. The potential of HCO₃^- as an antibiotic adjuvant is evident; its ability to increase virulence in pathogens such as Enterococcus faecalis and Mycobacterium tuberculosis requires meticulous scrutiny. HCO₃^- modulates bacterial behaviours in diverse manners: it promotes Escherichia coli O157:H7 colonization in the human gut by altering specific gene expression and, with Pseudomonas aeruginosa, amplifies the effect of tobramycin on planktonic cells while promoting biofilm formation. These multifaceted effects necessitate profound mechanistic exploration before HCO₃^- can be considered a promising clinical adjuvant.