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Four different genetic families of the enzyme carbonic anhydrase (CA, EC 4.2.1.1) are present in bacteria, α-, β-, γ- and ι-CAs. They play relevant functions related to CO 2 , HCO 3− /H +  ions homeostasis, being involved in metabolic biosynthetic pathways, pH regulation, and represent virulence and survival factors for bacteria in various niches. Bacterial CAs started to be considered druggable targets in the last decade, as their inhibition impairs survival, growth, and virulence of these pathogens. Significant advances were registered in the last years for designing effective inhibitors of sulfonamide type for  Helicobacter pylori  α-CA,  Neisseria gonorrhoeae  α-CA, vacomycin-resistant enterococci (VRE) α- and γ-CAs, for which the in vivo validation has also been achieved. MIC-s in the range of 0.25–4.0 µg/mL for wild type and drug resistant  N. gonorrhoeae  strains, and of 0.007–2.0 µg/mL for VRE were observed for some 1,3,4-thiadiazole-2-sulfonamides, and acetazolamide was effective in gut decolonization from VRE. Targeting bacterial CAs from other pathogens, among which  Vibrio cholerae ,  Mycobacterium tuberculosis ,  Brucella suis ,  Salmonella enterica  serovar Typhimurium,  Legionella pneumophila ,  Porphyromonas gingivalis ,  Clostridium perfringens ,  Streptococcus mutans ,  Burkholderia pseudomallei ,  Francisella tularensis ,  Escherichia coli ,  Mammaliicoccus (Staphylococcus) sciuri ,  Pseudomonas aeruginosa , may lead to novel antibacterials devoid of drug resistance problems.

An overview of novel antimicrobial carbonic anhydrase inhibitors