{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:29:37Z","timestamp":1791296977657,"version":"4.1.0"},"reference-count":50,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2009,12,1]],"date-time":"2009-12-01T00:00:00Z","timestamp":1259625600000},"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":[[2009,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p><jats:italic>Cryptococcus neoformans<\/jats:italic>serotype A strains, the major cause of cryptococcosis, are distributed worldwide, while serotype D strains are more concentrated in Central Europe. We have previously shown that deletion of the global regulator<jats:italic>TUP1<\/jats:italic>in serotype D isolates results in a novel peptide-mediated, density-dependent growth phenotype that mimics quorum sensing and is not known to exist in other fungi. Unlike for<jats:italic>tup1<\/jats:italic>\u0394 strains of serotype D, the density-dependent growth phenotype was found to be absent in<jats:italic>tup1<\/jats:italic>\u0394 strains of serotype A which had been derived from several different genetic clusters. The serotype A H99<jats:italic>tup1<\/jats:italic>\u0394 strain showed less retardation in the growth rate than<jats:italic>tup1<\/jats:italic>\u0394 strains of serotype D, but the mating efficiency was found to be similar in both serotypes. Deletion of<jats:italic>TUP1<\/jats:italic>in the H99 strain resulted in significantly enhanced capsule production and defective melanin formation and also revealed a unique regulatory role of the<jats:italic>TUP1<\/jats:italic>gene in maintaining iron\/copper homeostasis. Differential expression of various genes involved in capsule formation and iron\/copper homeostasis was observed between the wild-type and<jats:italic>tup1<\/jats:italic>\u0394 H99 strains. Furthermore, the H99<jats:italic>tup1<\/jats:italic>\u0394 strain displayed pleiotropic effects which included sensitivity to sodium dodecyl sulfate, susceptibility to fluconazole, and attenuated virulence. These results demonstrate that the global regulator<jats:italic>TUP1<\/jats:italic>has pathobiological significance and plays both conserved and distinct roles in serotype A and D strains of<jats:italic>C. neoformans<\/jats:italic>.<\/jats:p>","DOI":"10.1128\/ec.00256-09","type":"journal-article","created":{"date-parts":[[2009,10,10]],"date-time":"2009-10-10T01:24:23Z","timestamp":1255137863000},"page":"1901-1908","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":49,"title":["Regulatory Diversity of<i>TUP1<\/i>in<i>Cryptococcus neoformans<\/i>"],"prefix":"10.1128","volume":"8","author":[{"given":"Hyeseung","family":"Lee","sequence":"first","affiliation":[{"name":"Molecular Microbiology Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun C.","family":"Chang","sequence":"additional","affiliation":[{"name":"Molecular Microbiology Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashok","family":"Varma","sequence":"additional","affiliation":[{"name":"Molecular Microbiology Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung J.","family":"Kwon-Chung","sequence":"additional","affiliation":[{"name":"Molecular Microbiology Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e04-11-0987"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/156.1.31"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5322.105"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.14.7.4912-4919.1994"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.191.5.871"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1405.071312"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.1.173-180.2003"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.2.982-985.2000"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5338.680"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2001.tb00582.x"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00887-07"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2001.02332.x"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.3.1.14-26.2004"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.13.4.708"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.femsyr.2004.04.003"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2007.01077.x"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0040045"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0040410"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90146-4"},{"key":"e_1_3_2_21_2","unstructured":"Abstr. 15th Congr. 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