Abstract
Bacteria encode carbonic anhydrases (CAs, EC 4.2.1.1) belonging to three different genetic families, the α-, β-, and γ-classes. By equilibrating CO2 and bicarbonate, these metalloenzymes interfere with pH regulation and other crucial physiological processes of these organisms. The detailed investigations of many such enzymes from pathogenic and non-pathogenic bacteria afford the opportunity to design both novel therapeutic agents, as well as biomimetic processes, for example, for CO2 capture. Investigation of bacterial CA inhibitors and activators may be relevant for finding antibiotics with a new mechanism of action.
Highlights
In the time of emerging antibiotic resistance, the improvement of pharmacological arsenal against bacterial pathogens is of pivotal importance [1,2]
An example of the typical structural organization of a bacterial α-CA is offered by the X-ray crystal structure of the CA identified in the thermophilic bacterium Sulfurihydrogenibium yellowstonense YO3AOP1 (Figure 4) [30,33]
This three-dimensional structure generally resembles those of human α-CAs and it was obtained in the presence of the classical inhibitor of CAs, the sulfonamide acetazolamide (AAZ)
Summary
In the time of emerging antibiotic resistance, the improvement of pharmacological arsenal against bacterial pathogens is of pivotal importance [1,2]. The inhibition of the new bacterial targets takes place through mechanisms different from those usually represented by the block of DNA gyrase, the inhibition of the ribosomal function, and the shut down of the cell-wall biosynthesis, as most clinically used antibiotics act [3] This strategy will result in the development of new antiinfectives, which can replace those already used in clinics with increasing bacterial resistance. In this context, the superfamily of carbonic anhydrases (CAs, EC 4.2.1.1) represents a valuable member of such new macromolecules affecting the growth of microorganisms or making them vulnerable to the host defense mechanisms [4,5,6,7,8]. Thermophilic CAs are still active at high temperatures compared to their mesophilic counterparts, and their use is preferred in environments characterized by hard conditions, such as those of the carbon capture process (high temperature, high salinity, extreme pH) [18,19,20,21]
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