SELECTION OF THERAPEUTIC TARGETS AND/OR BIOMARKERS FROM GLOBAL RESPONSE TRANSCRIPTIONAL OF ALVEOLAR MACROPHAGES INFECTED BY H. capsulatum BIOFILMS

Abstract

Histoplasma capsulatum variety capsulatum is a fungal pathogen which causes histoplasmosis that occurs as a result of inhalation of microconidea from mycelial phase, primarily affecting the lung which occurs the yeast differentiation, inducing a pulmonary infection and dissemination to other organs. Recently, a correlation between the H. capsulatum infection mode, and the formation of biofilms was established. Additionally our group evaluated for the first time the miRNA expression profile in human macrophages infected with yeasts of the fungus on biofilm and planktonic form, and the results showed a differential response of the host cell compared to uninfected cells and compared to the biofilm mode. In this context, the formation of H. capsulatum biofilms has been associated with nosocomial infections and for this reason, is emerging the identification of differential biomarkers and target that may be selected in order to establish a new therapeutic approach for histoplasmosis. Based on this, this work aims to analyze the differential transcriptome between alveolar macrophages (Mø) infected with H. capsulatum yeast structured in biofilms and planktonic cultures, such that uninfected cells will be used as control. The complete sequencing of the transcribed regions will be performed using an Illumina platform to identify potential candidate genes that encoding key proteins and characterize the transcriptional signature of infection by H. caspulatum in its different forms of growth identifying biomarkers that show the existence of biofilms in the interaction H. capsulatum-host cells. (AU)