{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T22:24:31Z","timestamp":1791239071336,"version":"4.1.0"},"reference-count":47,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2003,10,1]],"date-time":"2003-10-01T00:00:00Z","timestamp":1064966400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Eukaryot Cell"],"published-print":{"date-parts":[[2003,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:italic>Cryptococcus neoformans<\/jats:italic>\n            is a human fungal pathogen that exists as three distinct varieties or sibling species: the predominantly opportunistic pathogens\n            <jats:italic>C. neoformans<\/jats:italic>\n            var.\n            <jats:italic>neoformans<\/jats:italic>\n            (serotype D) and\n            <jats:italic>C. neoformans<\/jats:italic>\n            var.\n            <jats:italic>grubii<\/jats:italic>\n            (serotype A) and the primary pathogen\n            <jats:italic>C. neoformans<\/jats:italic>\n            var.\n            <jats:italic>gattii<\/jats:italic>\n            (serotypes B and C). While serotypes A and D are cosmopolitan, serotypes B and C are typically restricted to tropical regions. However, serotype B isolates of\n            <jats:italic>C. neoformans<\/jats:italic>\n            var.\n            <jats:italic>gattii<\/jats:italic>\n            have recently caused an outbreak on Vancouver Island in Canada, highlighting the threat of this fungus and its capacity to infect immunocompetent individuals. Here we report a large-scale analysis of the mating abilities of serotype B and C isolates from diverse sources and identify unusual strains that mate robustly and are suitable for further genetic analysis. Unlike most isolates, which are of both the\n            <jats:bold>a<\/jats:bold>\n            and \u03b1 mating types but are predominantly sterile, the majority of the Vancouver outbreak strains are exclusively of the \u03b1 mating type and the majority are fertile. In an effort to enhance mating of these isolates, we identified and disrupted the\n            <jats:italic>CRG1<\/jats:italic>\n            gene encoding the GTPase-activating protein involved in attenuating pheromone response.\n            <jats:italic>crg1<\/jats:italic>\n            mutations dramatically increased mating efficiency and enabled mating with otherwise sterile isolates. Our studies provide a genetic and molecular foundation for further studies of this primary pathogen and reveal that the Vancouver Island outbreak may be attributable to a recent recombination event.\n          <\/jats:p>","DOI":"10.1128\/ec.2.5.1036-1045.2003","type":"journal-article","created":{"date-parts":[[2003,10,11]],"date-time":"2003-10-11T23:53:40Z","timestamp":1065916420000},"page":"1036-1045","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":262,"title":["Recapitulation of the Sexual Cycle of the Primary Fungal Pathogen\n            <i>Cryptococcus neoformans<\/i>\n            var.\n            <i>gattii<\/i>\n            : Implications for an Outbreak on Vancouver Island, Canada"],"prefix":"10.1128","volume":"2","author":[{"given":"James A.","family":"Fraser","sequence":"first","affiliation":[{"name":"Departments of Molecular Genetics and Microbiology"},{"name":"Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan L.","family":"Subaran","sequence":"additional","affiliation":[{"name":"Departments of Molecular Genetics and Microbiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Connie B.","family":"Nichols","sequence":"additional","affiliation":[{"name":"Departments of Molecular Genetics and Microbiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Heitman","sequence":"additional","affiliation":[{"name":"Departments of Molecular Genetics and Microbiology"},{"name":"Medicine"},{"name":"Pharmacology and Cancer Biology"},{"name":"Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi9729965"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M202254200"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(01)00408-5"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1086\/313992"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1080\/02681219680000691"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-148-8-2607"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1006\/fgbi.1999.1180"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.15.7.3635"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.70.1.703"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.28.7.1642-1644.1990"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1445-5994.1993.tb04726.x"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.35.9.2243-2251.1997"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1061888"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.37.9.2920-2926.1999"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.41.2.703-711.2003"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1006\/fgbi.1999.1155"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genet.36.052402.152652"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.25921-0"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.10.5478"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.64.2.316-353.2000"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1080\/00275514.1976.12019972"},{"key":"e_1_3_2_23_2","unstructured":"Kwon-Chung K. 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