{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T14:48:54Z","timestamp":1792075734543,"version":"4.4.0"},"reference-count":57,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2019,7,16]],"date-time":"2019-07-16T00:00:00Z","timestamp":1563235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,8,27]],"date-time":"2019-08-27T00:00:00Z","timestamp":1566864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI134636"],"award-info":[{"award-number":["R01AI134636"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U01AI089244"],"award-info":[{"award-number":["U01AI089244"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI123315"],"award-info":[{"award-number":["R01AI123315"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"HHS | NIH | National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R21NS108715"],"award-info":[{"award-number":["R21NS108715"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2019,8,27]]},"abstract":"<jats:p>\n                    Even with the best available care, mortality rates in cryptococcal meningitis range from 20% to 60%. Disease is often due to infection by the fungus\n                    <jats:named-content content-type=\"genus-species\">Cryptococcus neoformans<\/jats:named-content>\n                    and involves a complex interaction between the human host and the fungal pathogen. Although previous studies have suggested genetic differences in the pathogen impact human disease, it has proven quite difficult to identify the specific\n                    <jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>\n                    genes that impact the outcome of the human infection. Here, we take advantage of a Ugandan patient cohort infected with closely related\n                    <jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>\n                    strains to examine the role of pathogen genetic variants on several human disease characteristics. Using a pathogen whole-genome sequencing approach, we showed that 40\u2009\n                    <jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>\n                    genes are associated with human disease. Surprisingly, many of these genes are specific to\n                    <jats:italic>Cryptococcus<\/jats:italic>\n                    and have unknown functions. We also show deletion of some of these genes alters disease in a mouse model of infection, confirming their role in disease. These findings are particularly important because they are the first to identify\n                    <jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>\n                    genes associated with human cryptococcal meningitis and lay the foundation for future studies that may lead to new treatment strategies aimed at reducing patient mortality.\n                  <\/jats:p>","DOI":"10.1128\/mbio.01440-19","type":"journal-article","created":{"date-parts":[[2019,7,15]],"date-time":"2019-07-15T06:56:08Z","timestamp":1563173768000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":62,"title":["Identification of Pathogen Genomic Differences That Impact Human Immune Response and Disease during Cryptococcus neoformans Infection"],"prefix":"10.1128","volume":"10","author":[{"given":"Aleeza C.","family":"Gerstein","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Minnesota, Minneapolis, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrina M.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Minnesota, Minneapolis, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tami R.","family":"McDonald","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Minnesota, Minneapolis, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yina","family":"Wang","sequence":"additional","affiliation":[{"name":"Public Health Research Institute, Rutgers University, Newark, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin D.","family":"Lueck","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Minnesota, Minneapolis, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Bohjanen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Minnesota, Minneapolis, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle D.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Minnesota, Minneapolis, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Akampurira","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute and School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David B.","family":"Meya","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute and School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoyang","family":"Xue","sequence":"additional","affiliation":[{"name":"Public Health Research Institute, Rutgers University, Newark, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Boulware","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Minnesota, Minneapolis, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(17)30243-8"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a019752"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002870"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/jof2040029"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2016.05.010"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/yea.3222"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.07.046"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00768-06"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00196-12"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0003847"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.resmic.2014.04.001"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fbr.2012.02.004"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI72950"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fbr.2018.01.001"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiu441"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00311-15"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1155\/2009\/840452"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1522-2683(19990101)20:8<1790::AID-ELPS1790>3.0.CO;2-2"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00046-19"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0193237"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0005223"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0072222"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-10092-5"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.218727.116"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01299-15"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1312884"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004261"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI18309"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00073-13"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00084-10"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00327-10"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01087-13"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1521"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMsr1203730"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(10)70033-1"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0141974"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg.2016.118"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01982-07"},{"key":"e_1_3_2_40_2","doi-asserted-by":"crossref","unstructured":"Galardini M Busby BP Vieitez C Dunham AS Typas A Beltrao P. 2018. The impact of the genetic background on gene deletion phenotypes in Saccharomyces cerevisiae . bioRxiv doi:10.1101\/487439.","DOI":"10.1101\/487439"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0005628"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02016-18"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.01277-10"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiv067"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1000384"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01340-15"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.107524.110"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.806"},{"key":"e_1_3_2_49_2","first-page":"11.10.1","article-title":"From FastQ data to high confidence variant calls: the Genome Analysis Toolkit best practices pipeline","volume":"43","author":"Van der Auwera GA","year":"2002","unstructured":"Van der Auwera GA, Carneiro MO, Hartl C, Poplin R, Del Angel G, Levy-Moonshine A, Jordan T, Shakir K, Roazen D, Thibault J, Banks E, Garimella KV, Altshuler D, Gabriel S, DePristo MA. 2002. From FastQ data to high confidence variant calls: the Genome Analysis Toolkit best practices pipeline. Curr Protoc Bioinform 43:11.10.1\u201311.10.33.","journal-title":"Curr Protoc Bioinform"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu170"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp698"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.4161\/fly.19695"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-15-162"},{"key":"e_1_3_2_54_2","first-page":"453","article-title":"Activity of VT-1129 against Cryptococcus neoformans clinical isolates with high fluconazole MICs","volume":"55","author":"Nielsen K","year":"2017","unstructured":"Nielsen K, Vedula P, Smith KD, Meya DB, Garvey EP, Hoekstra WJ, Schotzinger RJ, Boulware DR. 2017. Activity of VT-1129 against Cryptococcus neoformans clinical isolates with high fluconazole MICs. Med Mycol 55:453\u2013456.","journal-title":"Med Mycol"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.55.3.742-748.1987"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.9.4831-4841.2003"},{"key":"e_1_3_2_57_2","unstructured":"Therneau TM. 2015. A package for survival analysis in S. https:\/\/CRAN.R-project.org\/package=survival."},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/69.3.553"}],"container-title":["mBio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mBio.01440-19","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mBio.01440-19","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T21:22:30Z","timestamp":1646688150000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/mBio.01440-19"}},"subtitle":[],"editor":[{"given":"J. Andrew","family":"Alspaugh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2019,8,27]]},"references-count":57,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2019,8,27]]}},"alternative-id":["10.1128\/mBio.01440-19"],"URL":"https:\/\/doi.org\/10.1128\/mbio.01440-19","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/592212","asserted-by":"object"}]},"ISSN":["2161-2129","2150-7511"],"issn-type":[{"value":"2161-2129","type":"print"},{"value":"2150-7511","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,8,27]]},"assertion":[{"value":"2019-06-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-06-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-07-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01440-19"}}