Author(s):
Bernardo, Ruben T. ; Cunha, Diana V. ; Wang, Can ; Pereira, L. P. ; Silva, Sónia Carina ; Salazar, Sara B. ; Schröder, Markus S. ; Okamoto, Michiyo ; Takahashi-Nakaguchi, Azusa ; Chibana, Hiroji ; Aoyama, Toshihiro ; Sá-Correia, Isabel ; Azeredo, Joana ; Butler, Geraldine ; Mira, Nuno Pereira
Date: 2017
Persistent ID: http://hdl.handle.net/1822/44462
Origin: RepositóriUM - Universidade do Minho
Project/scholarship:
info:eu-repo/grantAgreement/FCT/5876/147338/PT;
info:eu-repo/grantAgreement/FCT/5876-PPCDTI/120495/PT
;
info:eu-repo/grantAgreement/FCT/COMPETE/120495/PT;
Subject(s): CgHaa1; acetic acid; Candida glabrata; vaginal dysbiosis; vaginal candidiasis; Science & Technology
Description
To thrive in the acidic vaginal tract C. glabrata has to cope with high concentrations of acetic acid. The mechanisms underlying C. glabrata tolerance to acetic acid at low pH remain largely uncharacterized. In this work it is demonstrated the essential role of the CgHaa1 transcription factor (encoded by ORF CAGL0L09339g) in the response and tolerance of C. glabrata to acetic acid. Transcriptomic analysis showed that CgHaa1 regulates, directly or indirectly, the expression of about 75% of the genes activated under acetic acid stress. CgHaa1-activated targets are involved in multiple physiological functions including membrane transport, metabolism of carbohydrates and amino acids, regulation of the activity of the plasma membrane H+-ATPase and adhesion. Under acetic acid stress CgHaa1 increased the activity and the expression of the CgPma1 proton pump and contributed to increased colonization of vaginal epithelial cells by C. glabrata. CgHAA1, CgTPO3 and CgHSP30, two identified CgHaa1-activated targets, are herein demonstrated to be determinants of C. glabrata tolerance to acetic acid. The protective effect of CgTpo3 and of CgHaa1 was linked to a role of these proteins in reducing the accumulation of acetic acid inside C. glabrata cells. In response to acetic acid stress, marked differences were found in the regulons controlled by CgHaa1 and by its S. cerevisiae ScHaa1 ortholog, demonstrating a clear divergent evolution of the two regulatory networks. The results gathered in this study significantly advance the understanding of the molecular mechanisms underlying the success of C. glabrata as a vaginal colonizer.
Cristoph Schueller (University of Natural Resources and Life Sciences, Austria) and Ken Haynes (University of Exeter, UK) are acknowledged for sharing strains. Funding received by the Institute for Bioengineering and Biosciences from the Portuguese Foundation for Science and Technology (FCT) (UID/BIO/04565/2013) and from Programa Operacional Regional de Lisboa 2020 (project no. 007317)is acknowledged. FCT is also acknowledged for funding the Centre of Biological Engineering through contracts FCOMP-01-0124-FEDER020243 and PTDC/EBB-EBI/120495/2010. Science Foundation Ireland and the Wellcome Trust are acknowledged for funding G.B.
