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An Overview of the Carbonic Anhydrases from Two Pathogens of the Oral Cavity: Streptococcus mutans and Porphyromonas gingivalis

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CURRENT TOPICS IN MEDICINAL CHEMISTRY
卷 16, 期 21, 页码 2359-2368

出版社

BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1568026616666160413135522

关键词

Carbonic anhydrase; Inhibitor; Sulfonamide; Anion; Oral cavity; Pathogen; Streptococcus mutans; Porphyromonas gingivalis

资金

  1. FP6 and FP7 EU projects (DeZnIt, Gums and Joints, and Dynano)

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Among the crowd of bacteria provoking disease of the oral cavity during the weakened of immune system, Streptococcus mutans and Porphyromonas gingivalis are the main microorganisms implicated in caries formation and periodontitis, respectively. The life cycle of the pathogens, such as protozoa, fungi and bacteria, is influenced by a superfamily of enzymes, called carbonic anhydrases (CAs, EC 4.2.1.1). These metalloenzymes, being crucial for the survival of the pathogen, have been considered as novel anti-infective targets. In fact, bicarbonate and protons, produced by the CA catalyzed carbon dioxide as substrate, are two fundamental ions implicated in the pH regulation, biosynthetic reactions, and adaptation of the pathogen to the host or in the possibility of the pathogen to avoid the host immune system. Bacteria genome encodes for the alpha-, beta- and gamma-CAs. Recently, our groups using the recombinant DNA technology prepared and characterized the CAs belonging to the beta- and gamma-classes encoded by the genome of the two oral cavity pathogens S. mutans and P. gingivalis. An extensive inhibition study was carried out using typical anion/sulfonamide inhibitors of these classes of CAs. We discovered numerous inhibitors, which had in vitro an effective inhibitory activity against the bacterial CAs considered, here, as alternative anti-infective targets.

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