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Carbonic anhydrase regulation and CO2 sensing in the fungal pathogen Candida glabrata involves a novel Rca1p ortholog

Cottier, Fabien, Leewattanapasuk, Worraanong, Kemp, Laura R., Murphy, Mariana, Supuran, Claudiu T., Kurzai, Oliver, Mühlschlegel, Fritz A. (2013) Carbonic anhydrase regulation and CO2 sensing in the fungal pathogen Candida glabrata involves a novel Rca1p ortholog. Bioorganic & Medicinal Chemistry, 21 (6). pp. 1549-1554. ISSN 0968-0896. (doi:10.1016/j.bmc.2012.05.053) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided) (KAR id:33348)

The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided.
Official URL:
http://dx.doi.org/10.1016/j.bmc.2012.05.053

Abstract

Carbon dioxide (CO2) is a ubiquitous gas present at 0.0391% in atmospheric air and 5.5% in human blood. It forms part of numerous carboxylation and decarboxylation reactions carried out in every cell. Carbonic anhydrases (CA) enhance the hydration of CO2 to generate bicarbonate, which is subsequently used in cellular metabolism. In microorganisms, including the yeasts Candida albicans and Saccharomyces cerevisiae, inactivation of CA leads to a growth defect in air, which is complemented in an atmosphere enriched with CO2. In this study we characterize the CA from the fungal pathogen of humans Candida glabrata, CgNce103p, and report a comparable phenotype following its inactivation. Furthermore, we show that expression of the C. glabrata CA is strongly regulated by environmental CO2 at both the protein and transcript level. Similar to what we have previously reported for C. albicans and S. cerevisiae, C. glabrata CA regulation by CO2 is independent from the cAMP-PKA pathway and requires the novel bZIP transcription factor CgRca1p. We show that CgRca1p is an ortholog of the transcription factors Rca1p from C. albicans and Cst6p from S. cerevisiae and prove that CA induction in low CO2 involves the conserved DNA-binding motif TGACGTCA located on this C. glabrata promoter. However, in contrast to what is found in C. albicans CgRca1p expression itself is not affected by CO2. Although our results suggest a high level of similarity between the CO2 sensing pathways from C. glabrata, S. cerevisiae and C. albicans, they also point out significant intrinsic differences.

Item Type: Article
DOI/Identification number: 10.1016/j.bmc.2012.05.053
Uncontrolled keywords: Fungal carbonic anhydrases; CO2 sensing; Carbonic anhydrase regulation
Subjects: Q Science
Divisions: Divisions > Division of Natural Sciences > Biosciences
Depositing User: Susan Davies
Date Deposited: 07 Mar 2013 15:44 UTC
Last Modified: 05 Nov 2024 10:16 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/33348 (The current URI for this page, for reference purposes)

University of Kent Author Information

Mühlschlegel, Fritz A..

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