Carbonic anhydrase and bacterial metabolism: a chance for antibacterial drug discovery

Introduction: Carbonic anhydrases (CAs, EC 4.2.1.1) play a pivotal role in the regulation of carbon dioxide, bicarbonate, and hydrogen ions within bacterial cells, ensuring pH homeostasis and facilitating energy production. We conducted a systematic literature search (PubMed, Web of Science, and Google Scholar) to examine the intricate interplay between CAs and bacterial metabolism, revealing the potential of CA inhibitors (CAIs) as innovative therapeutic agents against pathogenic bacteria. Area covered: Inhibition of bacterial CAs was explored in various pathogens, emphasizing the CA roles in microbial virulence, survival, and adaptability. Escherichia coli, a valid and convenient model microorganism, was recently used to investigate the effects of acetazolamide (AAZ) on the bacterial life cycle. Furthermore, the effectiveness of CAIs against pathogenic bacteria has been further substantiated for Vancomycin-Resistant Enterococci (VRE) and antibiotic-resistant Neisseria gonorrhoeae strains. Expert opinion: CAIs target bacterial metabolic pathways, offering alternatives to conventional therapies. They hold promise against drug-resistant microorganisms such as VRE and N.gonorrhoeae strains. CAIs offer promising avenues for addressing antibiotic resistance and underscore their potential as novel antibacterial agents. Recognizing the central role of CAs in bacterial growth and pathogenicity will pave the way for innovative infection control and treatment strategies possibly also for other antibiotic resistant species.