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Patient outcome depends on the interaction between the pathogen and the host. Understanding the mechanisms that C. neoformans uses to facilitate adaptation to the host and promote pathogenesis is necessary to better predict disease severity and establish proper treatment. Several virulence phenotypes have been characterized in C. neoformans, but the field still lacks a complete understanding of how genotype and phenotype contribute to clinical outcome. Furthermore, while it is known that C. neoformans genotype impacts patient outcome, the mechanisms remain unknown. This lack of understanding may be due to the genetic heterogeneity of C. neoformans and the extensive phenotypic variation observed between and within isolates during infection. In this review, we summarize the current understanding of how the various genotypes and phenotypes observed in C. neoformans correlate with human disease progression in the context of patient outcome and recurrence. We also postulate the mechanisms underlying the genetic and phenotypic changes that occur in vivo to promote rapid adaptation in the host.<\/jats:p>","DOI":"10.1042\/bsr20190337","type":"journal-article","created":{"date-parts":[[2020,10,6]],"date-time":"2020-10-06T09:36:39Z","timestamp":1601976999000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["The interplay of phenotype and genotype in<i>Cryptococcus neoformans<\/i>disease"],"prefix":"10.1042","volume":"40","author":[{"given":"Sophie","family":"Altamirano","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrina\u00a0M.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2318-168X","authenticated-orcid":false,"given":"Kirsten","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2020,10,16]]},"reference":[{"key":"2021111620301529800_B1","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.fgb.2015.02.009","article-title":"Recognition of seven species in the Cryptococcus gattii\/Cryptococcus neoformans species complex","volume":"78","author":"Hagen","year":"2015","journal-title":"Fungal Genet. 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