Transcriptional response of Fusarium oxysporum and Neocosmospora solani challenged with amphotericin B or posaconazole

Abstract

<jats:p>Some species of fusaria are well-known pathogens of humans, animals and plants. <jats:italic>Fusarium oxysporum</jats:italic> and <jats:italic>Neocosmospora solani</jats:italic> (formerly <jats:italic>Fusarium solani</jats:italic>) 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 <jats:italic>F. oxysporum</jats:italic> and <jats:italic>N. solani</jats:italic> 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 (<jats:italic>ERG5</jats:italic>), the sterol 24-C-methyltransferase (<jats:italic>ERG6</jats:italic>) gene, the glutathione S-transferase (<jats:italic>GST</jats:italic>) gene and of several members of the major facilitator superfamily (<jats:italic>MSF</jats:italic>) was demonstrated in this study after treating <jats:italic>F. oxysporum</jats:italic> 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.</jats:p>

Mycobiome in the Middle Ear Cavity with and Without Otitis Media with Effusion

“…The genus Candida is the most common fungus resulting in different invasive infections ( 27 ). Recently, human infections caused by F. oxysporum and F. solani (Neocosmospora solani ) have increased and become the second most common mold infections after aspergillosis ( 28 ). Although their mean relative abundance was too low (less than 2%) Aspergillus ( A. ruber ) and Rhizopus ( R. arrhizus ) were significantly more abundant in Group 2 than in Group 1 (p-values, 0.000).…”

Evidence for the Role of CYP51A and Xenobiotic Detoxification in Differential Sensitivity to Azole Fungicides in Boxwood Blight Pathogens

“…Of particular interest is a cytochrome P450 gene described as a benzoate-4-monooxygenase, which showed significant overexpression (g8537). A previous study on antifungal response in Fusarium oxysporum and Neocosmospora solani found a benzoate-4-monooxygenase to be overexpressed following treatment with amphotericin b and posoconazole [38]. This gene, denoted CYP53, is a member of the family of CYP450 enzymes exclusive to fungi that are involved in phenolic detoxification.…”

A One Health Perspective to Recognize <em>Fusarium</em> and <em>Neocosmospora</em> as Important in Clinical Practice

“…Furthermore, it was reported recently that several genes of F. oxysporum and F. solani related to mechanisms of antifungal resistance such as ergosterol synthesis pathways, drug efflux pumps, response to oxidative stress, and cell wall biosynthesis, were differentially regulated upon the treatment with amphotericin B (AMB) and posaconazole (PSC) [102].…”