Sulphonamide inhibition profile of Staphylococcus aureus β-carbonic anhydrase

This paper presents the production and kinetic and inhibitory characterisation of beta-carbonic anhydrase from the opportunistic bacterium Staphylococcus aureus (SauBCA). From the eight different carbonic anhydrase (CA) families known to date, humans have only the alpha-form, whereas many clinically relevant pathogens have beta- and/or gamma-form(s). Based on this discovery, beta- and gamma-CAs have been introduced as promising new anti-infective targets. The results of this study revealed that recombinant SauBCA possesses significant CO2 hydration activity with a k(cat) of 1.46 x 10(5) s(-1)and a k(cat)/K-M of 2.56 x 10(7) s(- 1)M(-1). Its enzymatic function was inhibited by various sulphonamides in the nanomolar - micromolar range, and the K-i of acetazolamide was 628 nM. The best inhibitor was the clinically used sulfamide agent famotidine (K-i of 71 nM). The least efficient inhibitors were zonisamide and dorzolamide. Our work encourages further investigations of SauBCA in an attempt to discover novel drugs against staphylococcal infections.