Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Transcriptome Analysis Unveils Gln3 Role in Amino Acids Assimilation and Fluconazole Resistance in Candida glabrata

  • Santos, Francisco J. Perez-de los (Unidad de Genomica Avanzada, Laboratorio Nacional de Genomica para la Biodiversidad (Langebio)) ;
  • Garcia-Ortega, Luis Fernando (Unidad de Genomica Avanzada, Laboratorio Nacional de Genomica para la Biodiversidad (Langebio)) ;
  • Robledo-Marquez, Karina (Division de Biologia Molecular, Instituto Potosino de Investigacion Científica y Tecnologica A. C. (IPICYT)) ;
  • Guzman-Moreno, Jesus (Division de Biologia Molecular, Instituto Potosino de Investigacion Científica y Tecnologica A. C. (IPICYT)) ;
  • Riego-Ruiz, Lina (Division de Biologia Molecular, Instituto Potosino de Investigacion Científica y Tecnologica A. C. (IPICYT))
  • Received : 2020.12.17
  • Accepted : 2021.04.19
  • Published : 2021.05.28
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Abstract

After Candida albicans, Candida glabrata is one of the most common fungal species associated with candidemia in nosocomial infections. Rapid acquisition of nutrients from the host is important for the survival of pathogens which possess the metabolic flexibility to assimilate different carbon and nitrogen compounds. In Saccharomyces cerevisiae, nitrogen assimilation is controlled through a mechanism known as Nitrogen Catabolite Repression (NCR). NCR is coordinated by the action of four GATA factors; two positive regulators, Gat1 and Gln3, and two negative regulators, Gzf3 and Dal80. A mechanism in C. glabrata similar to NCR in S. cerevisiae has not been broadly studied. We previously showed that in C. glabrata, Gln3, and not Gat1, has a major role in nitrogen assimilation as opposed to what has been observed in S. cerevisiae in which both factors regulate NCR-sensitive genes. Here, we expand the knowledge about the role of Gln3 from C. glabrata through the transcriptional analysis of BG14 and gln3Δ strains. Approximately, 53.5% of the detected genes were differentially expressed (DEG). From these DEG, amino acid metabolism and ABC transporters were two of the most enriched KEGG categories in our analysis (Up-DEG and Down-DEG, respectively). Furthermore, a positive role of Gln3 in AAA assimilation was described, as was its role in the transcriptional regulation of ARO8. Finally, an unexpected negative role of Gln3 in the gene regulation of ABC transporters CDR1 and CDR2 and its associated transcriptional regulator PDR1 was found. This observation was confirmed by a decreased susceptibility of the gln3Δ strain to fluconazole.

Keywords

Acknowledgement

The authors are grateful to Dr. Alejandro De Las Penas for kindly providing the pdr1𝚫 mutant, to Dr. Jorge C. Navarro-Munoz for preliminary data analysis and to Dr. Nicolas Gomez-Hernandez (IPICYT) for his skillful technical assistance. This study was funded by the Consejo Nacional de Ciencia y Tecnologia (CONACYT) grant CB-2009-132377 to LRR. LFGO and JGM received postdoctoral fellowships from CONACYT. KARM and FJPS received postdoctoral fellowships from IPICYT. The authors also gratefully acknowledge the computing time granted by the IPICYT Supercomputing National Center for Education & Research (CNS-IPICYT), grant TKIIR2020-LFGO.

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