Mid 1/Cch 1/Yvc 1 calcium channels are involved in Aspergillus fumigatus virulence

Ref ID: 19616

Author:

PA de Castro1, J Chiaratto1, L Kretli1, VLP Bom1, GH Goldman1,2*

Author address:

1Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, Sao
Paulo, Brazil
2Laboratorio Nacional de Ciencia e Tecnologia do Bioetanol (CTBE), Campinas, Sao Paulo, Brazil

Full conference title:

6th Advances Against Aspergillosis 2014

Abstract:

Purpose:
Calcium-mediated signaling mechanisms are widely employed in eukaryotes and are implicated in
the regulation of diverse biological processes including gene expression, exocytosis, cytoskeletal
rearrangement, cell morphology and in fungal pathogenesis. Although the high affinity Ca+2 channel,
Cch1, and its subunit Mid1 have been investigated and evaluated in yeast and some filamentous
fungi, little is known about the function of their homologs in Aspergillus fumigatus.
Methods:
Here we have characterized the yeast homologues Cch1 (Afu1g11110), Mid1 (Afu5g05840) and
Yvc1 (Afu3g13490) in A. fumigates by using deletion analysis. We also investigated these mutants
in a murine model of immunosuppressed aspergillosis.
Results:
Both null mutants midA and cchA showed a reduced diameter of growth when compared to the
wild type. However, the 916;cchA mutant rescued its phenotype when grown in the presence of 200
mM of calcium. In contrast, the 916;midA mutant was sensitive to increasing concentrations of CaCl2.
The 916;cchA mutant is more sensitive to MnCl2 while 916;mid mutant showed increased sensitivity to
paraquat, LiCl and MnCl2 and the double mutant 916;midA 916;cchA behaved essentially like the 916;midA.
The 916;yvcA mutant exhibited phenotype identical to the wild type. qPCR analyses showed that
cchA and midA genes had increased mRNA accumulation in the wild type strain when exposed to
calcium, Congo Red and Calcofluor White, while the yvcA gene has increased mRNA accumulation
only when exposed to calcium and Calcofluor White.
Conclusion:
The three single null mutants showed attenuated virulence and reduced fungal burden in a murine
model of invasive pulmonary aspergillosis. These results strongly indicate that calcium channels are
important for A. fumigatus virulence.
Supported by FAPESP and CNPq, Brazil

Abstract Number: 141

Conference Year: 2014

Link to conference website: http://www.AAA2014.org

New link: NULL

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