Inhibition of Bacterial Carbonic Anhydrases as a Novel Approach to Escape Drug Resistance

Objective: The metalloenzymes carbonic anhydrases (CAs, EC 4.2.1.1) widespread in microorganisms and present as three genetically distinct families may be considered for the design of antiinfective agents with a different mechanism of action compared to the clinically used antibiotics. CAs are crucial for the life cycle of the pathogen, interfering with pH regulation and biosynthetic processes in which CO2 or bicarbonate are substrates. CA inhibition was shown to lead to debilitation or growth defects of several pathogenic bacteria.

Background: Clinically used antibiotics act through one of these four mechanisms: cell wall biosynthesis inhibition, inhibition of protein biosynthesis, interference with DNA and RNA synthesis and the folate pathway.