Transcriptional response of and challenged with amphotericin B or posaconazole Open Access

Abstract

Some species of fusaria are well-known pathogens of humans, animals and plants. and (formerly ) cause human infections that range from onychomycosis or keratitis to severe disseminated infections. In general, these infections are difficult to treat due to poor therapeutic responses in immunocompromised patients. Despite that, little is known about the molecular mechanisms and transcriptional changes responsible for the antifungal resistance in fusaria. To shed light on the transcriptional response to antifungals, we carried out the first reported high-throughput RNA-seq analysis for and that had been exposed to amphotericin B (AMB) and posaconazole (PSC). We detected significant differences between the transcriptional profiles of the two species and we found that some oxidation-reduction, metabolic, cellular and transport processes were regulated differentially by both fungi. The same was found with several genes from the ergosterol synthesis, efflux pumps, oxidative stress response and membrane biosynthesis pathways. A significant up-regulation of the C-22 sterol desaturase (), the sterol 24-C-methyltransferase () gene, the glutathione S-transferase () gene and of several members of the major facilitator superfamily () was demonstrated in this study after treating with AMB. These results offer a good overview of transcriptional changes after exposure to commonly used antifungals, highlights the genes that are related to resistance mechanisms of these fungi, which will be a valuable tool for identifying causes of failure of treatments.

Funding
This study was supported by the:
  • Colciencias (Award This work was supported by the Faculty of Sciences at Universidad de los Andes and the Departamento Administrativo de Ciencia, Tecnología e Innovación (Colciencias) agreement Nº RC 268-2010.)
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2020-07-09
2024-03-29
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