Author(s): Dinamarco, Taisa Magnani ; Freitas, Fernanda Zanolli [UNESP] ; Almeida, Ricardo S. ; Brown, Neil Andrew ; dos Reis, Thaila Fernanda ; Zambelli Ramalho, Leandra Naira ; Savoldi, Marcela ; Goldman, Maria Helena S. ; Bertolini, Maria Celia [UNESP] ; Goldman, Gustavo Henrique
Date: 2014
Persistent ID: http://hdl.handle.net/11449/25344
Origin: Oasisbr
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Aspergillus fumigatus is a primary and opportunistic pathogen, as well as a major allergen, of mammals. The Ca+2-calcineurin pathway affects virulence, morphogenesis and antifungal drug action in A. fumigatus. Here, we investigated three components of the A. fumigatus Ca+2-calcineurin pathway, pmcA,-B, and -C, which encode calcium transporters. We demonstrated that CrzA can directly control the mRNA accumulation of the pmcA-C genes by binding to their promoter regions. CrzA-binding experiments suggested that the 5'-CACAGCCAC-3' and 5'-CCCTGCCCC-3' sequences upstream of pmcA and pmcC genes, respectively, are possible calcineurin-dependent response elements (CDREs)-like consensus motifs. Null mutants were constructed for pmcA and -beta and a conditional mutant for pmcC demonstrating pmcC is an essential gene. The Delta pmcA and Delta pmcB mutants were more sensitive to calcium and resistant to manganese and cyclosporin was able to modulate the sensitivity or resistance of these mutants to these salts, supporting the interaction between calcineurin and the function of these transporters. The pmcA-C genes have decreased mRNA abundance into the alveoli in the Delta calA and Delta crzA mutant strains. However, only the A. fumigatus Delta pmcA was avirulent in the murine model of invasive pulmonary aspergillosis.
Lab Nacl Ciência & Tecnol Bioetanol CTBE, São Paulo, Brazil
Univ São Paulo, Fac Ciencias Farmaceut Ribeirao Preto, São Paulo, Brazil
Univ São Paulo, Fac Filosofia Ciencias & Letras Ribeirao Preto, São Paulo, Brazil
Univ São Paulo, Fac Med Ribeirao Preto, São Paulo, Brazil
Univ Londrina, Dept Microbiol, Londrina, Parana, Brazil
Univ Estadual Paulista, Inst Quim, São Paulo, Brazil
Univ Estadual Paulista, Inst Quim, São Paulo, Brazil
