title: Aspergillus fumigatus MADS-Box Transcription Factor rlmA Is Required for Regulation of the Cell Wall Integrity and Virulence.
abstract: The Cell Wall Integrity (CWI) pathway is the primary signaling cascade that controls the de novo synthesis of the fungal cell wall, and in Saccharomyces cerevisiae this event is highly dependent on the RLM1 transcription factor. Here, we investigated the function of RlmA in the fungal pathogen Aspergillus fumigatus We show that the ΔrlmA strain exhibits an altered cell wall organization in addition to defects related to vegetative growth and tolerance to cell wall-perturbing agents. A genetic analysis indicated that rlmA is positioned downstream of the pkcA and mpkA genes in the CWI pathway. As a consequence, rlmA loss-of-function leads to the altered expression of genes encoding cell wall-related proteins. RlmA positively regulates the phosphorylation of MpkA and is induced at both protein and transcriptional levels during cell wall stress. The rlmA was also involved in tolerance to oxidative damage and transcriptional regulation of genes related to oxidative stress adaptation. Moreover, the ΔrlmA strain had attenuated virulence in a neutropenic murine model of invasive pulmonary aspergillosis. Our results suggest that RlmA functions as a transcription factor in the A. fumigatus CWI pathway, acting downstream of PkcA-MpkA signaling and contributing to the virulence of this fungus.
authors.affiliation: Departamento de Genética e Evolução, Centro de Ciências Biológicas e da Saúde, Universidade Federal de São Carlos, 13565 São Carlos, São Paulo, Brazil.
authors.forename: Marina Campos
authors.initials: MC
authors.lastname: Rocha
authors.affiliation: Departamento de Genética e Evolução, Centro de Ciências Biológicas e da Saúde, Universidade Federal de São Carlos, 13565 São Carlos, São Paulo, Brazil.
authors.forename: João Henrique Tadini Marilhano
authors.initials: JH
authors.lastname: Fabri
authors.affiliation: Departamento de Genética e Evolução, Centro de Ciências Biológicas e da Saúde, Universidade Federal de São Carlos, 13565 São Carlos, São Paulo, Brazil.
authors.forename: Krissia
authors.initials: K
authors.lastname: Franco de Godoy
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Brazil.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Alves de Castro
authors.affiliation: Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, 14049 Ribeirão Preto, São Paulo, Brazil.
authors.forename: Juliana Issa
authors.initials: JI
authors.lastname: Hori
authors.affiliation: Departamento de Genética e Evolução, Centro de Ciências Biológicas e da Saúde, Universidade Federal de São Carlos, 13565 São Carlos, São Paulo, Brazil.
authors.forename: Anderson
authors.initials: A
authors.lastname: Ferreira da Cunha
authors.affiliation: Molecular Microbiology and Biotechnology, Institute of Biology, Leiden University, 2333 Leiden, The Netherlands.
authors.forename: Mark
authors.initials: M
authors.lastname: Arentshorst
authors.affiliation: Molecular Microbiology and Biotechnology, Institute of Biology, Leiden University, 2333 Leiden, The Netherlands.
authors.forename: Arthur F J
authors.initials: AF
authors.lastname: Ram
authors.affiliation: Molecular Microbiology and Biotechnology, Institute of Biology, Leiden University, 2333 Leiden, The Netherlands.
authors.forename: Cees A M J J
authors.initials: CA
authors.lastname: van den Hondel
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Brazil.
authors.forename: Gustavo Henrique
authors.initials: GH
authors.lastname: Goldman
authors.affiliation: Departamento de Genética e Evolução, Centro de Ciências Biológicas e da Saúde, Universidade Federal de São Carlos, 13565 São Carlos, São Paulo, Brazil imalavazi@ufscar.br.
authors.forename: Iran
authors.identifier: 0000-0002-4526-4961
authors.initials: I
authors.lastname: Malavazi
mesh_terms: D000818:Animals; D001228:Aspergillosis / Q000235:genetics* / Q000382:microbiology; D001232:Aspergillus fumigatus / Q000235:genetics* / Q000472:pathogenicity; D002473:Cell Wall / Q000235:genetics* / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D006801:Humans; D026161:MADS Domain Proteins / Q000235:genetics*; D051379:Mice; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics
chemical_list: D026161:MADS Domain Proteins; C095725:RLM1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors
keywords: Aspergillus fumigatus; cell wall integrity; mpkA; rlmA; virulence