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

ABSTRACT

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.

KEYWORDS:

• Bacteria
• carbonic anhydrase
• novel antibacterials
• CA inhibitors
• drug repurposing

Article highlights

• CA plays a crucial function in the regulation and utilization of CO₂

• CA catalyzes the reversible hydration of CO₂ to HCO₃⁻ and H⁺ ions.

• Bacterial CAs are players in the virulence arsenal of pathogenic microorganisms.

• CA inhibitors (CAIs) offer an alternative approach for curbing bacterial growth and virulence.

• CAIs interfere with the levels of CO₂ and HCO₃⁻ within bacterial cells.

• CAIs were repurposed to design potent agents against antibiotic-resistant strains.

• CAIs offer options for addressing the widespread antibiotic resistance problem.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contribution statement

Conceptualization, C.C.; writing – original draft preparation, C.C.; writing – review and editing, C.C.; C.S.; supervision, C.C. and C.S.

All authors have read and agreed to the published version of the manuscript.

Additional information

Funding

This paper was funded by the Italian Ministry of University and Research, project [FISR2019_04819 BacCAD].