Biochemical and functional characterization of the transcription factor rlmA and the interaction of PkcA and Hsp90 in the fungus Aspergillus fumigatus

• Grant number: 13/22375-6
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: March 01, 2014
• End date: December 31, 2017
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Principal Investigator: Iran Malavazi
• Grantee: Marina Campos Rocha
• Host Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil

Abstract

Aspergillus fumigatus is a filamentous fungus opportunistic pathogen responsible for several diseases human respiratory , including invasive pulmonary aspergillosis , which is the cause of infection risklife . CWI (via the integrity of the cell wall ) is a signaling cascade in activated cells fungal under conditions of stress and cell wall plays a role in tailoring several fungal pathogens in the human host. In many fungi, CWI is triggered by activation Protein kinase C ( PKC ) which is associated with activation of a cascade of MAP kinases which in turn leads to activation of a transcription factor that enables the transcription of genes related to maintaining the integrity of the cell wall and its redevelopment . Besides the cell wall , the thermotolerance is one of the most important virulence determinants for the establishment and maintenance of infection the pathogen in the host organism , since this gives the multiplication capacity of the fungus high temperature ( 37 p C ) causing deep mycoses by this fact . The " heat shock protein" HSP90 is one molecular chaperone known to be involved in thermal adaptation in other fungal organisms and stabilizes many proteins against stress caused by heat. Recently, our laboratory identified an interaction between Hsp90 and PkcA indicating the involvement of this functionality in the CWI . Thus, this work aims to expand the study of the CWI in A. fumigatus characterized by functional transcription factor rlmA A. fumigatus in order to establish their role in maintaining and enhancing the integrity of the cell wall. In order to identify genes related to synthesis and remodeling of the cell wall are controlled by rlmA tests will be performed microarray and ChIP-PCR. Additionally the nature of the genetic interaction between hsp90 and pkcA previously observed will characterized in order to understand the role of pkcA towards CWI and thermotolerance that body.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ROCHA, MARINA CAMPOS; DE GODOY, KRISSIA FRANCO; BANNITZ-FERNANDES, RENATA; MARILHANO FABRI, JOAO H. T.; FERRARI BARBOSA, MAYRA M.; DE CASTRO, PATRICIA ALVES; ALMEIDA, FAUSTO; GOLDMAN, GUSTAVO HENRIQUE; DA CUNHA, ANDERSON FERREIRA; NETTO, LUIS E. S.; et al. Analyses of the three 1-Cys Peroxiredoxins from Aspergillus fumigatus reveal that cytosolic Prx1 is central to H2O2 metabolism and virulence. SCIENTIFIC REPORTS, v. 8, AUG 17 2018. (14/16636-4, 16/03322-7, 15/17541-0, 13/22375-6)

ANNICK RIES, LAURE NICOLAS; ROCHA, MARINA CAMPOS; DE CASTRO, PATRICIA ALVES; SILVA-ROCHA, RAFAEL; SILVA, ROBERTO NASCIMENTO; FREITAS, FERNANDA ZANOLLI; DE ASSIS, LEANDRO JOSE; BERTOLINI, MARIA CELIA; MALAVAZI, IRAN; GOLDMAN, GUSTAVO H.. The Aspergillus fumigatus CrzA Transcription Factor Activates Chitin Synthase Gene Expression during the Caspofungin Paradoxical Effect. MBIO, v. 8, n. 3, MAY-JUN 2017. (16/12948-7, 12/23942-9, 13/22375-6)