{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:13:36Z","timestamp":1790813616483,"version":"4.1.0"},"reference-count":68,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2012,9,25]],"date-time":"2012-09-25T00:00:00Z","timestamp":1348531200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2012,11,1]],"date-time":"2012-11-01T00:00:00Z","timestamp":1351728000000},"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":["mBio"],"published-print":{"date-parts":[[2012,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    In sub-Saharan Africa, cryptococcal meningitis (CM) continues to be a predominant cause of AIDS-related mortality. Understanding virulence and improving clinical treatments remain important. To characterize the role of the fungal strain genotype in clinical disease, we analyzed 140\n                    <jats:italic>Cryptococcus<\/jats:italic>\n                    isolates from 111 Ugandans with AIDS and CM. Isolates consisted of 107 nonredundant\n                    <jats:named-content content-type=\"genus-species\">Cryptococcus neoformans<\/jats:named-content>\n                    var.\n                    <jats:italic>grubii<\/jats:italic>\n                    strains and 8\n                    <jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>\n                    var.\n                    <jats:italic>grubii\/neoformans<\/jats:italic>\n                    hybrid strains. Multilocus sequence typing (MLST) was used to characterize genotypes, yielding 15 sequence types and 4 clonal clusters. The largest clonal cluster consisted of 74 isolates. The results of Burst and phylogenetic analysis suggested that the\n                    <jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>\n                    var.\n                    <jats:italic>grubii<\/jats:italic>\n                    strains could be separated into three nonredundant evolutionary groups (Burst group 1 to group 3). Patient mortality was differentially associated with the different evolutionary groups (\n                    <jats:italic>P<\/jats:italic>\n                    = 0.04), with the highest mortality observed among Burst group 1, Burst group 2, and hybrid strains. Compared to Burst group 3 strains, Burst group 1 strains were associated with higher mortality (\n                    <jats:italic>P<\/jats:italic>\n                    = 0.02), exhibited increased capsule shedding (\n                    <jats:italic>P<\/jats:italic>\n                    = 0.02), and elicited a more pronounced Th\n                    <jats:sub>2<\/jats:sub>\n                    response during\n                    <jats:italic>ex vivo<\/jats:italic>\n                    cytokine release assays with strain-specific capsule stimulation (\n                    <jats:italic>P<\/jats:italic>\n                    = 0.02). The results of these analyses suggest that cryptococcal strain variation can be an important determinant of human immune responses and mortality.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>IMPORTANCE<\/jats:bold>\n                    <jats:named-content content-type=\"genus-species\">Cryptococcus neoformans<\/jats:named-content>\n                    is a common life-threatening human fungal pathogen that is responsible for an estimated 1 million cases of meningitis in HIV-infected patients annually. Virulence factors that are important in human disease have been identified, yet the impacts of the fungal strain genotype on virulence and outcomes of human infection remain poorly understood. Using an analysis of strain variation based on\n                    <jats:italic>in vitro<\/jats:italic>\n                    assays and clinical data from Ugandans living with AIDS and cryptococcal infection, we report that strain genotype predicts the type of immune response and mortality risk. These studies suggest that knowledge of the strain genotype during human infections could be used to predict disease outcomes and lead to improved treatment approaches aimed at targeting the specific combination of pathogen virulence and host response.\n                  <\/jats:p>","DOI":"10.1128\/mbio.00196-12","type":"journal-article","created":{"date-parts":[[2012,9,26]],"date-time":"2012-09-26T09:16:54Z","timestamp":1348651014000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":84,"title":["Cryptococcal Genotype Influences Immunologic Response and Human Clinical Outcome after Meningitis"],"prefix":"10.1128","volume":"3","author":[{"given":"Darin L.","family":"Wiesner","sequence":"first","affiliation":[{"name":"Department of Microbiology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oleksandr","family":"Moskalenko","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer M.","family":"Corcoran","sequence":"additional","affiliation":[{"name":"Department of Forest Resources, University of Minnesota, St. Paul, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tami","family":"McDonald","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa A.","family":"Rolfes","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA"},{"name":"Center for Infectious Disease and Microbiology Translational Research, University of Minnesota, Minneapolis, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David B.","family":"Meya","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA"},{"name":"Infectious Disease Institute, Makerere University, Kampala, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Kajumbula","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Makerere University, Kampala, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Kambugu","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA"},{"name":"Infectious Disease Institute, Makerere University, Kampala, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul R.","family":"Bohjanen","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA"},{"name":"Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA"},{"name":"Center for Infectious Disease and Microbiology Translational Research, University of Minnesota, Minneapolis, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph F.","family":"Knight","sequence":"additional","affiliation":[{"name":"Department of Forest Resources, University of Minnesota, St. Paul, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Boulware","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA"},{"name":"Center for Infectious Disease and Microbiology Translational Research, University of Minnesota, Minneapolis, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA"},{"name":"Center for Infectious Disease and Microbiology Translational Research, University of Minnesota, Minneapolis, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","volume-title":"World AIDS Day Report","author":"Joint United Nations Programme on HIV\/AIDS","year":"2011","unstructured":"Joint United Nations Programme on HIV\/AIDSUNAIDS. 2011. World AIDS Day Report. Joint United Nations Programme on HIV\/AIDS (U.N. AIDS), Geneva, Switzerland."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e328322ffac"},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","unstructured":"BoulwareDR . 2010. Clinical features and serum biomarkers in HIV immune reconstitution inflammatory syndrome after cryptococcal meningitis: a prospective cohort study. PLoS Med. 7:e1000384. http:\/\/dx.doi.org\/10.1371\/journal.pmed.1000384.","DOI":"10.1371\/journal.pmed.1000384"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0b013e3181a56f2e"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.femsim.2005.06.005"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1080\/mmy.38.6.407.417"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.57.7.1922-1927.1989"},{"key":"e_1_3_2_9_2","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.4049\/jimmunol.129.4.1675","article-title":"The capsule of Cryptococcus neoformans passively inhibits phagocytosis of the yeast by macrophages","volume":"129","author":"Kozel TR","year":"1982","unstructured":"KozelTR GotschlichEC . 1982. The capsule of Cryptococcus neoformans passively inhibits phagocytosis of the yeast by macrophages. J. Immunol. 129:1675\u20131680.","journal-title":"J. Immunol"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.10.6445-6455.2001"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.3.1746"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.2.1027"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2009.080598"},{"key":"e_1_3_2_14_2","volume-title":"Janeway\u2019s immunobiology","author":"Murphy K","year":"2011","unstructured":"MurphyK . 2011. Janeway\u2019s immunobiology, 8th ed. Garland Science, New York, NY.","edition":"8"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.10.6064-6073.2001"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.187.16.5709-5718.2005"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.02596-05"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.01438-07"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2010.04.001"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2010.03222.x"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cir723"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/9781555818241"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/9781555816858"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1080\/13693780902953886"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.105.046672"},{"key":"e_1_3_2_26_2","doi-asserted-by":"crossref","unstructured":"Desnos-OllivierM . 2010. Mixed infections and in vivo evolution in the human fungal pathogen Cryptococcus neoformans. mBio. 1:e00091-10. http:\/\/dx.doi.org\/10.1128\/journal.pmed.00091-10.","DOI":"10.1128\/mBio.00091-10"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.186.5.1518-1530.2004"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1439-0507.1968.tb03400.x"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.01277-10"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0019688"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.43.9.4766-4772.2005"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.33.1.99-102.1995"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.2.6.1162-1168.2003"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00168-08"},{"key":"e_1_3_2_35_2","doi-asserted-by":"crossref","first-page":"4529","DOI":"10.4049\/jimmunol.157.10.4529","article-title":"Afferent phase production of TNF-\u03b1 is required for the development of protective T cell immunity to Cryptococcus neoformans","volume":"157","author":"Huffnagle GB","year":"1996","unstructured":"HuffnagleGB . 1996. Afferent phase production of TNF-\u03b1 is required for the development of protective T cell immunity to Cryptococcus neoformans. J. Immunol. 157:4529\u20134536.","journal-title":"J. Immunol"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.11.6429"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.1996.14723.x"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.173.4.793"},{"key":"e_1_3_2_39_2","doi-asserted-by":"crossref","first-page":"3219","DOI":"10.4049\/jimmunol.142.9.3219","article-title":"Fungicidal activity of IFN-\u03b3-activated macrophages: extracellular killing of Cryptococcus neoformans","volume":"142","author":"Flesch IE","year":"1989","unstructured":"FleschIE SchwambergerG KaufmannSH . 1989. Fungicidal activity of IFN-\u03b3-activated macrophages: extracellular killing of Cryptococcus neoformans. J. Immunol. 142:3219\u20133224.","journal-title":"J. Immunol"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.17.6.2879"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.090634"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00809-09"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1080\/08830180213274"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.idc.2006.07.001"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.14.1.62-67.1976"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.5.4.491-498.1972"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.95.1.5-8.1968"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0020120"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.2.664-669.1998"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-8749(03)00116-3"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1006\/cimm.1999.1557"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2012.9"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12281-011-0064-8"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e3283536a93"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1086\/587667"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1086\/655785"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.9.4831-4841.2003"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.175.5.1405-1411.1993"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid0902.020246"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.60.2.602-605.1992"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1007\/s002940050366"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04220"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00328721"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.52.4.461-466.1946"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.01072-09"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.38.1.471-471.2000"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/22.22.4673"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.63.8.3131-3136.1995"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.1.115-122.2001"}],"container-title":["mBio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mBio.00196-12","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mBio.00196-12","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,25]],"date-time":"2023-06-25T19:29:22Z","timestamp":1687721362000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/mBio.00196-12"}},"subtitle":[],"editor":[{"given":"Tom","family":"Chiller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]},{"given":"John W.","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2012,11]]},"references-count":68,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2012,11]]}},"alternative-id":["10.1128\/mBio.00196-12"],"URL":"https:\/\/doi.org\/10.1128\/mbio.00196-12","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.717997706.793474251","asserted-by":"object"}]},"ISSN":["2161-2129","2150-7511"],"issn-type":[{"value":"2161-2129","type":"print"},{"value":"2150-7511","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,11]]},"assertion":[{"value":"2012-06-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-08-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-09-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00196-12"}}