- Vacuolar zinc transporter Zrc1 is required for detoxification of excess intracellular zinc in the human fungal pathogen Cryptococcus neoformans
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Minsu Cho , Guanggan Hu , Mélissa Caza , Linda C. Horianopoulos , James W. Kronstad , Won Hee Jung
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J. Microbiol. 2018;56(1):65-71. Published online January 4, 2018
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DOI: https://doi.org/10.1007/s12275-018-7475-y
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Zinc is an important transition metal in all living organisms
and is required for numerous biological processes. However,
excess zinc can also be toxic to cells and cause cellular stress.
In the model fungus Saccharomyces cerevisiae, a vacuolar zinc
transporter, Zrc1, plays important roles in the storage and
detoxification of excess intracellular zinc to protect the cell.
In this study, we identified an ortholog of the S. cerevisiae
ZRC1 gene in the human fungal pathogen Cryptococcus neoformans.
Zrc1 was localized in the vacuolar membrane in C.
neoformans, and a mutant lacking ZRC1 showed significant
growth defects under high-zinc conditions. These results suggested
a role for Zrc1 in zinc detoxification. However, contrary
to our expectation, the expression of Zrc1 was induced
in cells grown in zinc-limited conditions and decreased upon
the addition of zinc. These expression patterns were similar
to those of Zip1, the high-affinity zinc transporter in the plasma
membrane of C. neoformans. Furthermore, we used the
zrc1 mutant in a murine model of cryptococcosis to examine
whether a mammalian host could inhibit the survival of C.
neoformans using zinc toxicity. We found that the mutant
showed no difference in virulence compared with the wildtype
strain. This result suggests that Zrc1-mediated zinc detoxification
is not required for the virulence of C. neoformans,
and imply that zinc toxicity may not be an important aspect
of the host immune response to the fungus.
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Citations
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- MINIREVIEW] The cAMP/protein kinase A signaling pathway in pathogenic basidiomycete fungi: Connections with iron homeostasis
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Jaehyuk Choi , Won Hee Jung , James W. Kronstad
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J. Microbiol. 2015;53(9):579-587. Published online August 1, 2015
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DOI: https://doi.org/10.1007/s12275-015-5247-5
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422
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Abstract
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A number of pathogenic species of basidiomycete fungi are
either life-threatening pathogens of humans or major economic
pests for crop production. Sensing the host is a key
aspect of pathogen proliferation during disease, and signal
transduction pathways are critically important for detecting
environmental conditions and facilitating adaptation. This
review focuses on the contributions of the cAMP/protein
kinase A (PKA) signaling pathway in Cryptococcus neoformans,
a species that causes meningitis in humans, and Ustilago
maydis, a model phytopathogen that causes a smut disease on
maize. Environmental sensing by the cAMP/PKA pathway
regulates the production of key virulence traits in C. neoformans
including the polysaccharide capsule and melanin.
For U. maydis, the pathway controls the dimorphic transition
from budding growth to the filamentous cell type required
for proliferation in plant tissue. We discuss recent advances
in identifying new components of the cAMP/PKA pathway
in these pathogens and highlight an emerging theme that
pathway signaling influences iron acquisition.
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