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Furthermore, zinc may play an essential role in the infectiousness of microorganisms. Previously, we determined that functional zinc metabolism is associated with <jats:italic>Cryptococcus gattii<\/jats:italic> virulence. Here, we characterized the ZIP zinc transporters in this human pathogen. Transcriptional profiling revealed that zinc levels regulated the expression of the <jats:italic>ZIP1<\/jats:italic>, <jats:italic>ZIP2<\/jats:italic> and <jats:italic>ZIP3<\/jats:italic> genes, although only the <jats:italic>C. gattii<\/jats:italic> zinc transporter Zip1 was required for yeast growth under zinc-limiting conditions. To associate zinc uptake defects with virulence, the most studied cryptococcal virulence factors (i.e., capsule, melanin and growth at 37\u2009\u00b0C) were assessed in <jats:italic>ZIP<\/jats:italic> mutant strains; however, no differences were detected in these classical virulence-associated traits among the mutant and WT strains. Interestingly, higher levels of reactive oxygen species were detected in the <jats:italic>zip1<\/jats:italic>\u0394 and in the <jats:italic>zip1<\/jats:italic>\u0394 <jats:italic>zip2<\/jats:italic>\u0394 double mutants. In line with these phenotypic alterations, the <jats:italic>zip1<\/jats:italic>\u0394 <jats:italic>zip2<\/jats:italic>\u0394 double mutant displayed attenuated virulence in a murine model of cryptococcosis. Together, these results indicate that adequate zinc uptake is necessary for cryptococcal fitness and virulence.<\/jats:p>","DOI":"10.1038\/srep10104","type":"journal-article","created":{"date-parts":[[2015,5,7]],"date-time":"2015-05-07T14:31:49Z","timestamp":1431009109000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Effects of zinc transporters on Cryptococcus gattii virulence"],"prefix":"10.1038","volume":"5","author":[{"given":"Rafael de Oliveira","family":"Schneider","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camila","family":"Diehl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francine Melise","family":"dos Santos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Al\u00edcia Corbellini","family":"Piffer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ane Wichine Acosta","family":"Garcia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcos Iuri Roos","family":"Kulmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Augusto","family":"Schrank","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L\u00edvia","family":"Kmetzsch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marilene Henning","family":"Vainstein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charley C.","family":"Staats","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2015,5,7]]},"reference":[{"key":"BFsrep10104_CR1","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1097\/QAD.0b013e328322ffac","volume":"23","author":"BJ Park","year":"2009","unstructured":"Park, B. 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