title: Local silencing controls the oxidative stress response and the multidrug resistance in Candida glabrata.
abstract: In Candida glabrata, the sirtuins Sir2 and Hst1 control the expression of a wide number of genes including adhesins required for host colonization and niacin transporters needed for growth. Given that these sirtuins can be inactivated during infection, we asked if their inhibition could modify the response of C. glabrata to other stressful conditions. Here, we found that deletion of HST1 decreases susceptibility of C. glabrata to fluconazole and hydrogen peroxide. The transcription factor Pdr1 and the ABC transporter Cdr1 mediated the fluconazole resistance phenotype of the hst1Δ cells, whereas the transcriptional activator Msn4 and the catalase Cta1 are necessary to provide oxidative stress resistance. We show that the transcription factor Sum1 interacts with Hst1 and participate in the regulation of these genes. Interestingly, even though C. glabrata and Saccharomyces cerevisiae are closely related phylogenetically, deletion of HST1 decreased susceptibility to fluconazole and hydrogen peroxide only in C. glabrata but not in S. cerevisiae, indicating a different transcriptional control by two similar sirtuins. Our findings suggest that Hst1 acts as a regulator of stress resistance associated-genes.
authors: IPICYT, División de Biología Molecular, Instituto Potosino de Investigación Científica y Tecnológica, Camino a la Presa San José 2055, Lomas 4a sección, San Luis Potosí, 78216, México.
authors: Emmanuel
authors: E
authors: Orta-Zavalza
authors: Gehenna
authors: G
authors: Guerrero-Serrano
authors: Guadalupe
authors: G
authors: Gutiérrez-Escobedo
authors: Israel
authors: I
authors: Cañas-Villamar
authors: Jacqueline
authors: J
authors: Juárez-Cepeda
authors: Irene
authors: I
authors: Castaño
authors: Alejandro
authors: A
authors: De Las Peñas
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology; D041221:Candida glabrata / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D026141:Drug Resistance, Multiple, Fungal; D015725:Fluconazole / Q000494:pharmacology; D005656:Fungal Proteins / Q000378:metabolism*; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D006861:Hydrogen Peroxide / Q000633:toxicity; D018384:Oxidative Stress; D025941:Protein Interaction Mapping; D037761:Sirtuins / Q000378:metabolism*; D013312:Stress, Physiological; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D005656:Fungal Proteins; D014157:Transcription Factors; D015725:Fluconazole; D006861:Hydrogen Peroxide; D037761:Sirtuins