Biomedical applications of prokaryotic carbonic anhydrases

ABSTRACT

Introduction: The hydration/dehydration of CO₂ catalyzed by carbonic anhydrases (CAs, EC 4.2.1.1) is a crucial physiological reaction for the survival of all living organisms because it is connected with numerous biosynthetic and biochemical pathways requiring CO₂ or HCO₃⁻, such as respiration, photosynthesis, carboxylation reactions, pH homeostasis, secretion of electrolytes, transport of CO₂, bicarbonate, etc.

Areas covered: The bacterial genome encodes CAs belonging to the α-, β-, and γ-CA classes able to ensure the survival and/or satisfying the metabolic needs of the bacteria, as demonstrated by in vivo and in vitro experiments. The discovery of new anti-infectives that target new bacterial pathways, such as those involving CAs, may lead to effective therapies against diseases subject to the antibiotic resistance. This aspect is important in pharmaceutical and biomedical research but received little attention till recently.

Expert opinion: An overview of the potential use of CAs in biomedical applications, as drug targets, bioindicators, and within artificial organs is presented. The discovery of thermostable bacterial CAs allowed the use of CAs in biotechnological applications, but patents related to the use of bacterial CAs in the development of pharmacological agents are scarce.

KEYWORDS:

• Carbonic anhydrases
• metalloenzymes
• bacteria
• anti-infectives
• biomedical application
• CA inhibition
• CA activation
• thermostable CA

Article highlights

• The bacterial genome encodes for CAs belonging to the α-, β-, and γ-CA classes.

• The α-CA is able to convert the CO₂ to bicarbonate diffused in the periplasmic space of the Gram-negative bacteria, while the β- or γ-CA classes have a cytoplasmic localization and are responsible for CO₂ supply for carboxylase enzymes, pH homeostasis and other intracellular functions.

• The growth of Ralstonia eutropha and Escherichia coli is strictly correlated to the CA activity; the two CAs (α and β) encoded by the genome of the pathogen Helicobacter pylori are essential for the acid acclimatization of the pathogen within the human stomach; Vibrio cholera uses its CAs (α, β and γ) for inducing cholera toxin expression; Brucella suis and the Mycobacterium tuberculosis needed of functional CAs for growing.

• The structural differences between the bacterial and human CAs offer the possibility to design specific inhibitors targeting the bacterial enzyme and not the human CAs.

• The discovery of new anti-infectives that target new bacterial pathways, such as those involving CAs, is essential for an effective therapy against diseases subject to the antibiotic resistance.

• The activation studies of the prokaryotic CAs will give new insights for understanding the role of the CAs in the survival and virulence of the microorganism.

• The discovery of CAs in microorganisms from extreme environments exhibit great potential as bioindicators, for example, they could be employed in detecting the leaks of CO₂ from the storage area.

• Thermostable bacterial CAs could be a valid solution for the realization of a more efficient artificial lung

This box summarizes key points contained in the article.

Declaration of interest

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.

Additional information

Funding

This paper was not funded.