title: The putative flavin carrier family FlcA-C is important for Aspergillus fumigatus virulence.
abstract: Aspergillus fumigatus is an opportunistic fungal pathogen and the most important species causing pulmonary fungal infections. The signaling by calcium is very important for A. fumigatus pathogenicity and it is regulated by the transcription factor CrzA. We have previously used used ChIP-seq (Chromatin Immunoprecipitation DNA sequencing) aiming to identify gene targets regulated by CrzA. We have identified among several genes regulated by calcium stress, the putative flavin transporter, flcA. This transporter belongs to a small protein family composed of FlcA, B, and C. The ΔflcA null mutant showed several phenotypes, such as morphological defects, increased sensitivity to calcium chelating-agent ethylene glycol tetraacetic acid (EGTA), cell wall or oxidative damaging agents and metals, repre-sentative of deficiencies in calcium signaling and iron homeostasis. Increasing calcium concentrations improved significantly the ΔflcA growth and conidiation, indicating that ΔflcA mutant has calcium insufficiency. Finally, ΔflcA-C mutants showed reduced flavin adenine dinucleotide (FAD) and were avirulent in a low dose murine infection model.
authors.affiliation: a Faculdade de Ciências Farmacêuticas de Ribeirão Preto and Faculdade de Medicina de Ribeirão Preto , Universidade de São Paulo , Ribeirão Preto , Brazil.
authors.forename: Patrícia A
authors.initials: PA
authors.lastname: de Castro
authors.affiliation: a Faculdade de Ciências Farmacêuticas de Ribeirão Preto and Faculdade de Medicina de Ribeirão Preto , Universidade de São Paulo , Ribeirão Preto , Brazil.
authors.forename: Jéssica
authors.initials: J
authors.lastname: Chiaratto
authors.affiliation: a Faculdade de Ciências Farmacêuticas de Ribeirão Preto and Faculdade de Medicina de Ribeirão Preto , Universidade de São Paulo , Ribeirão Preto , Brazil.
authors.forename: Enyara Rezende
authors.initials: ER
authors.lastname: Morais
authors.affiliation: a Faculdade de Ciências Farmacêuticas de Ribeirão Preto and Faculdade de Medicina de Ribeirão Preto , Universidade de São Paulo , Ribeirão Preto , Brazil.
authors.forename: Thaila Fernanda
authors.initials: TF
authors.lastname: Dos Reis
authors.affiliation: b Department of Plant Pathology , The Ohio State University , Columbus , OH , USA.
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Mitchell
authors.affiliation: c Plant Biology and Crop Science, Rothamsted Research , Harpenden, Herts , UK.
authors.forename: Neil A
authors.initials: NA
authors.lastname: Brown
authors.affiliation: a Faculdade de Ciências Farmacêuticas de Ribeirão Preto and Faculdade de Medicina de Ribeirão Preto , Universidade de São Paulo , Ribeirão Preto , Brazil.
authors.forename: Gustavo H
authors.initials: GH
authors.lastname: Goldman
mesh_terms: D000818:Animals; D001228:Aspergillosis / Q000382:microbiology; D001232:Aspergillus fumigatus / Q000187:drug effects / Q000235:genetics* / Q000472:pathogenicity*; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism; D005415:Flavins / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics*; D015966:Gene Expression Regulation, Fungal; D000073658:Loss of Function Mutation; D051379:Mice; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D014774:Virulence
chemical_list: C530975:CrzA protein, Aspergillus fumigatus; D005415:Flavins; D005656:Fungal Proteins; D014157:Transcription Factors; D005182:Flavin-Adenine Dinucleotide; D004533:Egtazic Acid; D002118:Calcium
keywords: Aspergillus fumigatus; CrzA; FAD metabolism; calcium; putative flavin flcA-C transporter family