Functional characterization of an Aspergillus fumigatus calcium transporter (PmcA) that is essential for fungal infection

Taísa Magnani Dinamarco, Fernanda Zanolli Freitas, Ricardo S. Almeida, Neil Andrew Brown, Thaila Fernanda dos Reis, Leandra Naira Zambelli Ramalho, Marcela Savoldi, Maria Helena S. Goldman, Maria Célia Bertolini, Gustavo Henrique Goldman

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34 Citations (Scopus)

Abstract

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 -B and a conditional mutant for pmcC demonstrating pmcC is an essential gene. The ΔpmcA and ΔpmcB 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 ΔcalA and ΔcrzA mutant strains. However, only the A. fumigatus ΔpmcA was avirulent in the murine model of invasive pulmonary aspergillosis.

Original languageEnglish
Article numbere37591
JournalPLoS ONE
Volume7
Issue number5
DOIs
Publication statusPublished - 23 May 2012

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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    Dinamarco, T. M., Freitas, F. Z., Almeida, R. S., Brown, N. A., dos Reis, T. F., Ramalho, L. N. Z., Savoldi, M., Goldman, M. H. S., Bertolini, M. C., & Goldman, G. H. (2012). Functional characterization of an Aspergillus fumigatus calcium transporter (PmcA) that is essential for fungal infection. PLoS ONE, 7(5), [e37591]. https://doi.org/10.1371/journal.pone.0037591