The CgHaa1-regulon mediates response and tolerance to acetic acid stress in the human pathogen Candida glabrata

• Autor(a) principal: Bernardo, Ruben T.
• Data de Publicação: 2017
• Outros Autores: 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
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/1822/44462
• topic: CgHaa1; acetic acid; Candida glabrata; vaginal dysbiosis; vaginal candidiasis; Science & Technology

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.