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Previous work revealed that the <jats:styled-content style=\"fixed-case\">ESCRT<\/jats:styled-content> (endosomal sorting complex required for transport) protein Vps23 functions in iron acquisition, capsule formation and virulence. Here, we further characterized the <jats:styled-content style=\"fixed-case\">ESCRT<\/jats:styled-content> machinery to demonstrate that defects in the <jats:styled-content style=\"fixed-case\">ESCRT\u2010II<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">III<\/jats:styled-content> complexes caused reduced capsule attachment, impaired growth on haem and resistance to non\u2010iron metalloprotoporphyrins. The <jats:styled-content style=\"fixed-case\">ESCRT<\/jats:styled-content> mutants shared several phenotypes with a mutant lacking the pH\u2010response regulator <jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>im101, and in other fungi, the <jats:styled-content style=\"fixed-case\">ESCRT<\/jats:styled-content> machinery is known to activate <jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>im101 via proteolytic cleavage. We therefore expressed a truncated and activated version of <jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>im101 in the <jats:styled-content style=\"fixed-case\">ESCRT<\/jats:styled-content> mutants and found that this allele restored capsule formation but not growth on haem, thus suggesting a <jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>im101\u2010independent contribution to haem uptake. We also demonstrated that the <jats:styled-content style=\"fixed-case\">ESCRT<\/jats:styled-content> machinery acts downstream of the c<jats:styled-content style=\"fixed-case\">AMP<\/jats:styled-content>\/protein kinase A pathway to influence capsule elaboration. Defects in the <jats:styled-content style=\"fixed-case\">ESCRT<\/jats:styled-content> components also attenuated virulence in macrophage survival assays and a mouse model of cryptococcosis to a greater extent than reported for loss of <jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>im101. Overall, these results indicate that the <jats:styled-content style=\"fixed-case\">ESCRT<\/jats:styled-content> complexes function in capsule elaboration, haem uptake and virulence via <jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>im101\u2010dependent and independent mechanisms.<\/jats:p>","DOI":"10.1111\/mmi.12985","type":"journal-article","created":{"date-parts":[[2015,3,3]],"date-time":"2015-03-03T04:13:10Z","timestamp":1425355990000},"page":"973-992","source":"Crossref","is-referenced-by-count":61,"title":["The endosomal sorting complex required for transport machinery influences haem uptake and capsule elaboration in <scp><i>C<\/i><\/scp><i>ryptococcus neoformans<\/i>"],"prefix":"10.1111","volume":"96","author":[{"given":"Guanggan","family":"Hu","sequence":"first","affiliation":[{"name":"Michael Smith Laboratories The University of British Columbia  2185 East Mall Vancouver BC V6T\u20091Z4 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