Title |
Vacuolar zinc transporter Zrc1 is required for detoxification of excess intracellular zinc in the human fungal pathogen Cryptococcus neoformans |
Author |
Minsu Cho1, Guanggan Hu2, Mélissa Caza2, Linda C. Horianopoulos2, James W. Kronstad2, and Won Hee Jung1* |
Address |
1Department of Systems Biotechnology, Chung-Ang University, Anseong 17546, Republic of Korea , 2Michael Smith Laboratories, University of British Columbia, Vancouver, B.C. V6T 1Z4, Canada |
Bibliography |
Journal of Microbiology, 56(1),65–71, 2018,
|
DOI |
10.1007/s12275-018-7475-y
|
Key Words |
Cryptococcus neoformans, vacuole, virulence, zinc, Zrc1 |
Abstract |
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. |