Proteomic and transcriptomic analysis of Histoplasma capsulatum biofilm and correlation with virulence factors in search of new therapeutic targets

Abstract

Histoplasma capsulatum var. capsulatum is a dimorphic fungus that causes histoplasmosis, a respiratory and systemic mycosis. The development of disease depends on the ability of Histoplasma yeast to survive and replicate within alveolar macrophages. In this context, it is known that adherence to host cells is the first step in the colonization and is essential for the establishment of infection. In view of this, some microorganisms adhere to biological and non-biological surfaces to form biofilms. Based on the potential importance of biofilms for survival in the human host and in nature, this study is designed to investigate the biofilm formation by H. capsulatum correlated with their ability to adhere to and/or invade epithelial cells and macrophages. Additionally, there will be an analysis of the proteome and transcriptome reveal that the protein and transcriptional profile differential fungus shaped biofilm and planktonic conditions under. Also set particularities of interaction between host cell and H. capsulatum shaped biofilm and select natural substances of plant origin capable of interfering in the formation of biofilm and the infection of the fungus to host cells. The antifungal substances can interfere with the structure or the destruction of the biofilm and the infection pathogen-host will be selected from collections of natural antifungal molecules obtained in collaboration as Project FAPESP Biota and CNPq Sisbiota with the Institute of Chemistry, UNESP Araraquara. (AU)