{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T03:40:42Z","timestamp":1794368442449,"version":"4.9.0"},"reference-count":65,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2003,9,1]],"date-time":"2003-09-01T00:00:00Z","timestamp":1062374400000},"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":["Infect Immun"],"published-print":{"date-parts":[[2003,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Cryptococcus neoformans<\/jats:italic>\n                    is a human-pathogenic fungus that has evolved into three distinct varieties that infect most prominently the central nervous system. A sexual cycle involving haploid cells of a and \u03b1 mating types has been reported for two varieties (\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>gattii<\/jats:italic>\n                    , serotypes B and C), yet the vast majority of infections involve a distinct variety (\n                    <jats:italic>C. neoformans<\/jats:italic>\n                    var.\n                    <jats:italic>grubii<\/jats:italic>\n                    , serotype A) that has been thought to be clonal and restricted to the \u03b1 mating type. We recently identified the first serotype A isolate of the a mating type which had been thought to be extinct (strain 125.91). Here we report that this unusual strain can mate with a subset of pathogenic serotype A strains to produce a filamentous dikaryon with fused clamp connections, basidia, and viable recombinant basidiospores. One meiotic segregant mated poorly with the serotype A reference strain H99 but robustly with a\n                    <jats:italic>crg1<\/jats:italic>\n                    mutant that lacks a regulator of G protein signaling and is hyperresponsive to mating pheromone. This meiotic segregant was used to create congenic a and \u03b1 mating type serotype A strains. Virulence tests with rabbit and murine models of cryptococcal meningitis showed that the serotype A congenic a and \u03b1 mating type strains had equivalent virulence in animal models, in contrast to previous studies linking the \u03b1 mating type to increased virulence in congenic serotype D strains. Our studies highlight a role for sexual recombination in the evolution of a human fungal pathogen and provide a robust genetic platform to establish the molecular determinants of virulence.\n                  <\/jats:p>","DOI":"10.1128\/iai.71.9.4831-4841.2003","type":"journal-article","created":{"date-parts":[[2003,8,21]],"date-time":"2003-08-21T17:40:43Z","timestamp":1061487643000},"page":"4831-4841","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":391,"title":["Sexual Cycle of\n                    <i>Cryptococcus neoformans<\/i>\n                    var.\n                    <i>grubii<\/i>\n                    and Virulence of Congenic\n                    <b>a<\/b>\n                    and \u03b1 Isolates"],"prefix":"10.1128","volume":"71","author":[{"given":"Kirsten","family":"Nielsen","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":"Gary M.","family":"Cox","sequence":"additional","affiliation":[{"name":"Departments of Molecular Genetics and Microbiology"},{"name":"Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Wang","sequence":"additional","affiliation":[{"name":"Departments of Molecular Genetics and Microbiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dena L.","family":"Toffaletti","sequence":"additional","affiliation":[{"name":"Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Perfect","sequence":"additional","affiliation":[{"name":"Departments of Molecular Genetics and Microbiology"},{"name":"Medicine"}],"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":"10.1101\/gad.11.23.3206"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-308X(08)60516-3"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.26.14473"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5385.1986"},{"key":"e_1_3_2_6_2","unstructured":"Bell G. 1982. The masterpiece of nature: the evolution and genetics of sexuality. University of California Press Berkeley."},{"key":"e_1_3_2_7_2","first-page":"337","volume":"54","year":"2000","unstructured":"Burt, A. 2000. Sex, recombination, and the efficacy of selection\u2014was Weismann right? Evolution Int. J. Org. Evolution54:337-351.","journal-title":"Evolution Int. J. Org. Evolution"},{"key":"e_1_3_2_8_2","first-page":"311","volume":"3","year":"2002","unstructured":"Butlin, R. 2002. Evolution of sex: the costs and benefits of sex: new insights from old asexual lineages. Nat. Rev. Genet.3:311-317.","journal-title":"Nat. Rev. Genet."},{"key":"e_1_3_2_9_2","unstructured":"Calderone R. A. 2002. Candida and candidiasis. American Society for Microbiology Washington D.C."},{"key":"e_1_3_2_10_2","doi-asserted-by":"crossref","unstructured":"Casadevall A. and J. R. Perfect. 1998. Cryptococcus neoformans . American Society for Microbiology Washington D.C.","DOI":"10.1128\/9781555818241"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.2.1.11-20.1982"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1420-9101.2001.00254.x"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.6.4101"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-148-8-2607"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(87)90166-8"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.35.9.2243-2251.1997"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.24.11591"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.22.12473"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1061888"},{"key":"e_1_3_2_20_2","unstructured":"Hawkesworth D. L. P. M. Kirk B. C. Sutton and D. N. Pegler. 1995. Ainsworth and Bisby's dictionary of the fungi 8th ed. International Mycology Institute Surrey United Kingdom."},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1006\/fgbi.1999.1155"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/101.3-4.519"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1041402"},{"key":"e_1_3_2_24_2","doi-asserted-by":"crossref","unstructured":"Hull C. M. and J. Heitman. 2002. Fungal mating: Candida albicans flips a switch to get in the mood. Curr. Biol. 12 : R782-R784.","DOI":"10.1016\/S0960-9822(02)01293-9"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genet.36.052402.152652"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.289.5477.307"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.25921-0"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1080\/00275514.1976.12019959"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1080\/00275514.1975.12019866"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00399484"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.60.2.602-605.1992"},{"key":"e_1_3_2_32_2","unstructured":"Kwon-Chung K. J. and J. E. Bennett. 1992. Cryptococcosis. Lea and Febiger Malvern Pa."},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a112628"},{"key":"e_1_3_2_34_2","unstructured":"Kwon-Chung K. J. and W. B. Hill. 1981. Sexuality and pathogenicity of Filobasidiella neoformans ( Cryptococcus neoformans ) p. 243-250. In R. Vanbreuseghem and C. DeVroy (ed.) Sexuality and pathogenicity of fungi. Masson Paris France."},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.1.115-122.2001"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.1.5.704-718.2002"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.26.14455"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1066241"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.289.5477.310"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1080\/mmy.39.1.151.154"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00837-1"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1080\/mmy.40.6.593.595"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.232568599"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1007\/s000360050113"},{"key":"e_1_3_2_45_2","first-page":"39","volume":"67","year":"1997","unstructured":"Roux, K. H., and K. H. Hecker. 1997. One-step optimization using touchdown and stepdown PCR. Methods Mol. Biol.67:39-45.","journal-title":"Methods Mol. Biol."},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.81002"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00436523"},{"key":"e_1_3_2_48_2","first-page":"133","volume":"5","year":"1981","unstructured":"Schmeding, K. A., S. C. Jong, and R. Hugh. 1981. Sexual compatibility between serotypes of Filobasidiella neoformans (Cryptococcus neoformans). Curr. Biol.5:133-138.","journal-title":"Curr. Biol."},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1006\/fgbi.2000.1192"},{"key":"e_1_3_2_50_2","unstructured":"Smith J. M. 1978. The evolution of sex. Cambridge University Press Cambridge United Kingdom."},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.261418798"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1078035"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1080\/02681219880000661"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.12.1.126"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.175.5.1405-1411.1993"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1080\/mmy.39.5.383.386"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.1.2.257-272.2002"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.1.352-362.2000"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.111144598"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.14.7327"},{"key":"e_1_3_2_61_2","unstructured":"Wickes B. L. and K. J. Kwon-Chung. 2002. Genetic basis of pathogenicity in Cryptococcus neoformans p. 25-49. In R. A. Calderone and R. L. Cihlar (ed.) Fungal pathogenesis: principles and clinical applications vol. 14. Marcel Dekker New York N.Y."},{"key":"e_1_3_2_62_2","unstructured":"Williams G. C. 1975. Sex and recombination. Princeton University Press Princeton N.J."},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1006\/fgbi.2001.1311"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/162.3.1157"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-294X.1999.00523.x"},{"key":"e_1_3_2_66_2","unstructured":"Xu J. and T. G. Mitchell. 2002. Strain variation and clonality in Candida spp. and Cryptococcus neoformans p. 739-749. In R. A. Calderone and R. L. Cihlar (ed.) Fungal pathogenesis: principles and clinical applications vol. 14. Marcel Dekker New York N.Y."}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.71.9.4831-4841.2003","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.71.9.4831-4841.2003","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T23:22:39Z","timestamp":1646436159000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/IAI.71.9.4831-4841.2003"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,9]]},"references-count":65,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2003,9]]}},"alternative-id":["10.1128\/IAI.71.9.4831-4841.2003"],"URL":"https:\/\/doi.org\/10.1128\/iai.71.9.4831-4841.2003","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1015308.196354","asserted-by":"object"}]},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,9]]},"assertion":[{"value":"2003-03-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2003-04-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2003-09-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}