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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,1,10]]},"abstract":"<jats:p>\n                    A pet cockatoo was the suspected source of\n                    <jats:italic>Cryptococcus neoformans<\/jats:italic>\n                    recovered from an immunocompromised patient with cryptococcosis based on molecular analyses available in 2000. Here, we report whole genome sequence analysis of the clinical and cockatoo strains. Both are closely related MAT\u03b1 strains belonging to the VNII lineage, confirming that the human infection likely originated from pet bird exposure. The two strains differ by 61 single nucleotide polymorphisms, including eight nonsynonymous changes involving seven genes. To ascertain whether changes in these genes are selected for during mammalian infection, we passaged the cockatoo strain in mice. Remarkably, isolates obtained from mouse tissue possess a frameshift mutation in one of the seven genes altered in the human sample (LQVO5_000317), a gene predicted to encode an SWI\u2013SNF chromatin-remodeling complex protein. In addition, both cockatoo and patient strains as well as mouse-passaged isolates obtained from brain tissue had a premature stop codon in a homologue of ZFC3 (LQVO5_004463), a predicted single-zinc finger containing protein, which is associated with larger capsules when deleted and reverted to a full-length protein in the mouse-passaged isolates obtained from lung tissue. The patient strain and mouse-passaged isolates show variability in virulence factors, with differences in capsule size, melanization, rates of nonlytic expulsion from macrophages, and amoeba predation resistance. Our results establish that environmental strains undergo genomic and phenotypic changes during mammalian passage, suggesting that animal virulence can be a mechanism for genetic change and that the genomes of clinical isolates may provide a readout of mutations acquired during infection.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2217111120","type":"journal-article","created":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T13:42:37Z","timestamp":1672926157000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":22,"title":["Similar evolutionary trajectories in an environmental\n                    <i>Cryptococcus neoformans<\/i>\n                    isolate after human and murine infection"],"prefix":"10.1073","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1103-6028","authenticated-orcid":false,"given":"Poppy","family":"Sephton-Clark","sequence":"first","affiliation":[{"name":"Broad Institute of MIT and Harvard, Cambridge, MA 02142"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott A.","family":"McConnell","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Grossman","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9970-6278","authenticated-orcid":false,"given":"Rosanna P.","family":"Baker","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quigly","family":"Dragotakes","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunfan","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5376-7243","authenticated-orcid":false,"given":"Man Shun","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gracen","family":"Gerbig","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth","family":"Greengo","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Marie","family":"Hardwick","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhura","family":"Kulkarni","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart M.","family":"Levitz","sequence":"additional","affiliation":[{"name":"Department of Medicine, UMass Chan Medical School, Worcester, MA 01605"},{"name":"Department of Microbiology and Physiological Systems, UMass Chan Medical School, Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua D.","family":"Nosanchuk","sequence":"additional","affiliation":[{"name":"Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461"},{"name":"Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7276-7786","authenticated-orcid":false,"given":"Shmuel","family":"Shoham","sequence":"additional","affiliation":[{"name":"Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7674-9988","authenticated-orcid":false,"given":"Daniel F. Q.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Stempinski","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2083-6027","authenticated-orcid":false,"given":"Winston","family":"Timp","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maggie P.","family":"Wear","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5778-960X","authenticated-orcid":false,"given":"Christina A.","family":"Cuomo","sequence":"additional","affiliation":[{"name":"Broad Institute of MIT and Harvard, Cambridge, MA 02142"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9402-9167","authenticated-orcid":false,"given":"Arturo","family":"Casadevall","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2023,1,5]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1128\/9781555818241"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.107.5.e66"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI136223"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.32.5.1188-1192.1994"},{"key":"e_1_3_4_5_2","article-title":"Genomic epidemiology of a Cryptococcus neoformans case cluster in Glasgow, Scotland, 2018","volume":"7","author":"Farrer R. 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