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Aspergillus fumigatus  is a major opportunistic pathogen and allergen of mammals. Calcium homeostasis and signaling is essential for numerous biological processes and also influences  A. fumigatus  pathogenicity. The presented study characterized the function of the  A. fumigatus  homologues of three  Saccharomyces cerevisiae  calcium channels, voltage-gated Cch1, stretch-activated Mid1 and vacuolar Yvc1. The  A. fumigatus  calcium channels  cchA ,  midA  and  yvcA  were regulated at transcriptional level by increased calcium levels. The YvcA::GFP fusion protein localized to the vacuoles. Both  ΔcchA  and  ΔmidA  mutant strains showed reduced radial growth rate in nutrient-poor minimal media. Interestingly, this growth defect in the  ΔcchA  strain was rescued by the exogenous addition of CaCl 2 . The  ΔcchA ,  ΔmidA , and  ΔcchA ΔmidA  strains were also sensitive to the oxidative stress inducer, paraquat. Restriction of external Ca 2+  through the addition of the Ca 2+ -chelator EGTA impacted upon the growth of the  ΔcchA  and  ΔmidA  strains. All the  A. fumigatus ΔcchA ,  ΔmidA , and  ΔyvcA  strains demonstrated attenuated virulence in a neutropenic murine model of invasive pulmonary aspergillosis. Infection with the parental strain resulted in a 100% mortality rate at 15 days post-infection, while the mortality rate of the  ΔcchA ,  ΔmidA , and  ΔyvcA  strains after 15 days post-infection was only 25%. Collectively, this investigation strongly indicates that CchA, MidA, and YvcA play a role in  A. fumigatus  calcium homeostasis and virulence.

The Involvement of the Mid1/Cch1/Yvc1 Calcium Channels in Aspergillus fumigatus Virulence