Transcriptome-wide survey of gene expression changes and alternative splicing in Trichophyton rubrum in response to undecanoic acid

Author(s)

Mendes, Niege S. ^[1] ; Bitencourt, Tamires A. ^[1] ; Sanches, Pablo R. ^[1] ; Silva-Rocha, Rafael ^[2] ; Martinez-Rossi, Nilce M. ^[1] ; Rossi, Antonio ^[1]

Affiliation

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Genet, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Mol & Cellular Biol, BR-14049900 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 8, FEB 6 2018.
• Web of Science Citations: 6

Abstract

While fatty acids are known to be toxic to dermatophytes, key physiological aspects of the Trichophyton rubrum response to undecanoic acid (UDA), a medium chain saturated fatty acid (C-11:0), are not well understood. Thus, we analysed RNA-seq data from T. rubrum exposed to sub-lethal doses of UDA for 3 and 12 h. Three putative pathways were primarily involved in UDA detoxification: lipid metabolism and cellular membrane composition, oxidative stress, and pathogenesis. Biochemical assays showed cell membrane impairment, reductions in ergosterol content, and an increase in keratinolytic activity following UDA exposure. Moreover, we assessed differential exon usage and intron retention following UDA exposure. A key enzyme supplying guanine nucleotides to cells, inosine monophosphate dehydrogenase (IMPDH), showed high levels of intron 2 retention. Additionally, phosphoglucomutase (PGM), which is involved in the glycogen synthesis and degradation as well as cell wall biosynthesis, exhibited a significant difference in exon 4 usage following UDA exposure. Owing to the roles of these enzymes in fungal cells, both have emerged as promising antifungal targets. We showed that intron 2 retention in impdh and exon 4 skipping in pgm might be related to an adaptive strategy to combat fatty acid toxicity. Thus, the general effect of UDA fungal toxicity involves changes to fungal metabolism and mechanisms for regulating pre-mRNA processing events. (AU)

• FAPESP's process: 14/03847-7 - Molecular characterization of mechanisms involved in pathogenicity and cell signaling in fungi
• Grantee: Nilce Maria Martinez-Rossi
• Support type: Research Projects - Thematic Grants
• FAPESP's process: 15/23435-8 - Molecular mechanisms involved in resistance and adaptive response to fungal inhibitors
• Grantee: Tamires Aparecida Bitencourt
• Support type: Scholarships in Brazil - Post-Doctorate