Expression of genes related to the cell wall from dimorphic pathogenic fungi under stress conditions: identification of involved transcription factors

Abstract

Paracoccidioides species and Histoplasma capsulatum are medically important thermodimorphic fungi. The cell wall, which is the main interface of the fungus with the host, is constituted mainly of structural polysaccharides, which are remodelled during stress conditions. This project aims to study, under different stress conditions, the global expression regulation of transcription factors as Adr1, Hsf e Rlm1, and genes related to synthesis/remodelling of the main cell wall polysaccharides from P. brasiliensis (Pb3 and Pb18), P. lutzii, and H. capsulatum. Composition of the cell wall polysaccharides will be analyzed in parallel. We intend to recognize a co-regulatory pattern of gene expression (e.g., chitin synthases, chitinases, alpha and beta glucan synthases, glucanases, beta mannosidases, alfa galactosidases, glucosamine-fructose-6-phosphate-aminotransferase, phosphoacetylglucosamine mutase, rho2, and beta-1,3-glucanosyltransferase) and identify transcription factors involved in global regulation in each stress condition. The importance of selected transcription factors and mapping of transcription elements in biology and virulence of mutants will be verified. Genetic manipulation of fungal isolates will be performed during a stay at Dr. Chad A. Rappleye's laboratory at The Ohio State University. We hope to improve the poor knowledge about transcriptional regulation to stress in dimorphs, thus helping to select new potential therapeutic targets. (AU)