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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Transcriptomic studies on Purpureocillium lilacinum reveal molecular mechanisms of response to fluconazole and itraconazole

Full text
Author(s):
Pedezzi, Rafael [1] ; de Biagi Junior, Carlos Alberto Oliveira [2] ; de Freitas, Marcela Cristina Correa [3] ; da Rosa-Garzon, Nathalia Gonsales [1] ; Cabral, Hamilton [1]
Total Authors: 5
Affiliation:
[1] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Pharmaceut Sci, BR-14040903 Ribeirao Preto - Brazil
[2] Univ Sao Paulo, Natl Inst Sci & Technol Stem Cell & Cell Therapy, Ribeirao Preto Med Sch, Dept Genet, BR-14049900 Ribeirao Preto - Brazil
[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Blood Ctr Ribeirao Preto, Dept Med Clin, BR-14049900 Ribeirao Preto - Brazil
Total Affiliations: 3
Document type: Journal article
Source: Brazilian Journal of Microbiology; v. 52, n. 2 MAR 2021.
Web of Science Citations: 0
Abstract

Filamentous fungus Purpureocillium lilacinum is an emerging pathogen that infects immunocompromised and immunocompetent individuals and is resistant to several azole molecules. Although azole resistance mechanisms are well studied in Aspergillus sp. and Candida sp., there are no studies to date reporting P. lilacinum molecular response to these molecules. The aim of this study was to describe P. lilacinum molecular mechanisms involved in antifungal response against fluconazole and itraconazole. Transcriptomic analyses showed that gene expression modulation takes place when P. lilacinum is challenged for 12 h with fluconazole (64 mu g/mL) or itraconazole (16 mu g/mL). The antifungals acted on the ergosterol biosynthesis pathway, and two homologous genes coding for cytochrome P450 51 enzymes were upregulated. Genes coding for efflux pumps, such as the major facilitator superfamily transporter, also displayed increased expression in the treated samples. We propose that P. lilacinum develops antifungal responses by raising the expression levels of cytochrome P450 enzymes and efflux pumps. Such modulation could confer P. lilacinum high levels of target enzymes and could lead to the constant withdrawal of antifungals, which would force an increase in the administration of antifungal medications to achieve fungal morbidity or mortality. The findings in this work could aid in the decision-making for treatment strategies in cases of P. lilacinum infection. (AU)

FAPESP's process: 15/16084-4 - Skopuleriopsis koningii enzyme prospection using proteome: Recombinant production of enzimes with biotecnological potential and evaluation of Antifungal
Grantee:Rafael Pedezzi
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 16/20385-2 - Obtaintion of heterologous peptidase for biochemical studies and biotechnological applications
Grantee:Hamilton Cabral
Support Opportunities: Regular Research Grants