Transcription factors and regulation of cell wall-related genes from Histoplasma capsulatum during stress

Abstract

Histoplasma capsulatum is a medically important thermodimorphic fungal species in North and Latin America. The cell wall, which is the main interface of the fungus with the host, is composed mainly of structural polysaccharides, which are remodeled during stress conditions. Many fungal transcription factors have been involved in the response to different stress conditions, including Mns2/4, Hsf1, Rlm1, Swi4, Adr1 and Crz1. During the Post-Doc project related to this BEPE application, we found that transcription elements recognized by Hsf and Adr1 transcription factors were abundant in promoter regions from all groups of cell wall polysaccharide-related genes. Accordingly, we showed that stress conditions caused by low pH and NaNO2 induced substantial changes in transcription factor and cell wall-related gene transcription profiles. Low pH increased the mRNA levels of genes encoding heat shock factor (Hsf), Msn2/4, Crz1, alpha and beta-glucan synthases, chitin synthase, chitinase, and beta-glucanase. On the other hand, nitrosative stress decreased mRNA levels of Crz1 and chitin synthase, beta-glucosidase and Rho1 GTPase. The present project aims to evaluate the functional importance of Histoplasma transcription factors in the regulation of cell wall-related genes during different stress and infection-related conditions. We will evaluate the role of transcription factors using knocked-down mutant strains by RNAi. We will also characterize the gene regulatory sequences by truncation and/or insertion of transcription element copies in cell wall-related gene promoters. This project will be carried out in the Ohio State University, Columbus, USA, under the supervision of Dr. Chad A. Rappleye. (AU)