Bacterial carbonic anhydrases

Carbonic anhydrases (CAs, EC 4.2.1.1) are metalloenzymes which catalyze the hydration of carbon dioxide to bicarbonate and protons. Many pathogenic bacteria encode such enzymes belonging to the α-, β-, and/or γ-CA families. In the last decade enzymes from Neisseria spp., Helicobacter pylori, Escherichia coli, Mycobacterium tuberculosis, Brucella spp., Streptococcus pneumoniae, Salmonella enterica, Haemophilus influenzae, Legionella pneumophila, Vibrio cholerae, Porphyromonas gingivalis, Streptococcus mutans, Clostridium perfringens, Pseudomonas aeruginosa, etc., have been cloned and characterized in detail. For some of these enzymes the X-ray crystal structures were determined, and in vitro/in vivo inhibition studies with various classes of inhibitors (e.g., anions, sulfonamides, and sulfamates) performed. For Neisseria spp., H. pylori, B. suis, and S. pneumoniae enzymes it has been possible to evidence inhibition of bacterial growth in vivo when inhibitors were present in the medium. Considering such preliminary results, bacterial CAs represent promising targets for obtaining antibacterials devoid of the resistance problems to the clinically used antibiotics, but further studies are granted for validating most of these enzymes as drug targets.