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The calcium transporter P mc1 provides C a 2+ tolerance and influences the progression of murine cryptococcal infection
Author(s) -
Kmetzsch Livia,
Staats Charley C.,
Cupertino Julia B.,
Fonseca Fernanda L.,
Rodrigues Marcio L.,
Schrank Augusto,
Vainstein Marilene H.
Publication year - 2013
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.12458
Subject(s) - cryptococcus neoformans , calcium , calcium signaling , cytosol , biology , virulence , microbiology and biotechnology , transporter , pathogenesis , calcium in biology , calcium metabolism , signal transduction , intracellular , biochemistry , chemistry , immunology , gene , enzyme , organic chemistry
The Ca 2+ ‐calcineurin signaling pathway in the human fungal pathogen Cryptococcus neoformans is essential for adaptation to the host environment during infection. Calcium transporters regulate cytosolic calcium concentrations, providing Ca 2+ loading into storage organelles. The three calcium transporters that have been characterized in C. neoformans , Cch1, Eca1 and Vcx1, are required for fungal virulence, supporting a role for calcium‐mediated signaling in cryptococcal pathogenesis. In the present study, we report the functional characterization of the putative vacuolar calcium ATP ase Pmc1 in C. neoformans . Our results demonstrate that Pmc1 provides tolerance to high Ca 2+ concentrations. The double knockout of C. neoformans PMC 1 and VCX 1 genes impaired the intracellular calcium transport, resulting in a significant increase in cytosolic calcium levels. Furthermore, Pmc1 was essential for both the progression of pulmonary infection and brain colonization in mice, emphasizing the crucial role of calcium signaling and transport for cryptococcal pathogenesis.