{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T22:58:50Z","timestamp":1790290730687,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1011763","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T00:00:00Z","timestamp":1701043200000}}],"reference-count":90,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T00:00:00Z","timestamp":1699833600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases, NIH","doi-asserted-by":"crossref","award":["R01AI133654"],"award-info":[{"award-number":["R01AI133654"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases, NIH","doi-asserted-by":"crossref","award":["R01AI39115"],"award-info":[{"award-number":["R01AI39115"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    The \u201cAmoeboid Predator-Fungal Animal Virulence Hypothesis\u201d posits that interactions with environmental phagocytes shape the evolution of virulence traits in fungal pathogens. In this hypothesis, selection to avoid predation by amoeba inadvertently selects for traits that contribute to fungal escape from phagocytic immune cells. Here, we investigate this hypothesis in the human fungal pathogens\n                    <jats:italic>Cryptococcus neoformans<\/jats:italic>\n                    and\n                    <jats:italic>Cryptococcus deneoformans<\/jats:italic>\n                    . Applying quantitative trait locus (QTL) mapping and comparative genomics, we discovered a cross-species QTL region that is responsible for variation in resistance to amoeba predation. In\n                    <jats:italic>C. neoformans<\/jats:italic>\n                    , this same QTL was found to have pleiotropic effects on melanization, an established virulence factor. Through fine mapping and population genomic comparisons, we identified the gene encoding the transcription factor Bzp4 that underlies this pleiotropic QTL and we show that decreased expression of this gene reduces melanization and increases susceptibility to amoeba predation. Despite the joint effects of\n                    <jats:italic>BZP4<\/jats:italic>\n                    on amoeba resistance and melanin production, we find no relationship between\n                    <jats:italic>BZP4<\/jats:italic>\n                    genotype and escape from macrophages or virulence in murine models of disease. Our findings provide new perspectives on how microbial ecology shapes the genetic architecture of fungal virulence, and suggests the need for more nuanced models for the evolution of pathogenesis that account for the complexities of both microbe-microbe and microbe-host interactions.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1011763","type":"journal-article","created":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T13:40:36Z","timestamp":1699882836000},"page":"e1011763","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":14,"title":["Amoeba predation of Cryptococcus: A quantitative and population genomic evaluation of the accidental pathogen hypothesis"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9524-2288","authenticated-orcid":true,"given":"Thomas J. C.","family":"Sauters","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cullen","family":"Roth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debra","family":"Murray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Floyd Averette","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chinaemerem U.","family":"Onyishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin C.","family":"May","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Heitman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7659-2589","authenticated-orcid":true,"given":"Paul M.","family":"Magwene","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,11,13]]},"reference":[{"key":"ppat.1011763.ref001","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1016\/j.tim.2012.04.005","article-title":"Evolution of virulence in opportunistic pathogens: Generalism, plasticity, and control","volume":"20","author":"SP Brown","year":"2012","journal-title":"Trends Microbiol"},{"key":"ppat.1011763.ref002","doi-asserted-by":"crossref","DOI":"10.1098\/rsfs.2019.0056","article-title":"On modelling environmentally transmitted pathogens","volume":"10","author":"C Lanzas","year":"2020","journal-title":"Interface Focus"},{"key":"ppat.1011763.ref003","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1146\/annurev.micro.61.080706.093305","article-title":"Evolution of intracellular pathogens","volume":"62","author":"A Casadevall","year":"2008","journal-title":"Annu Rev Microbiol"},{"key":"ppat.1011763.ref004","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0011882","article-title":"From grazing resistance to pathogenesis: The coincidental evolution of virulence factors","volume":"5","author":"S Adiba","year":"2010","journal-title":"PLoS ONE"},{"key":"ppat.1011763.ref005","first-page":"1","article-title":"Evolution of Bordetellae from environmental microbes to human respiratory pathogens: amoebae as a missing link","volume":"7","author":"DL Taylor-Mulneix","year":"2017","journal-title":"Front Cell Infect 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castellanii","volume":"121","author":"J Rizzo","year":"2017","journal-title":"Fungal Biology"},{"key":"ppat.1011763.ref040","doi-asserted-by":"crossref","first-page":"4862","DOI":"10.1128\/IAI.71.9.4862-4872.2003","article-title":"Cryptococcus neoformans virulence is enhanced after growth in the genetically malleable host Dictyostelium discoideum","volume":"71","author":"JN Steenbergen","year":"2003","journal-title":"Infect Immun"},{"key":"ppat.1011763.ref041","first-page":"1","article-title":"Cryptococcus neoformans mating and genetic crosses","volume":"53","author":"S Sun","year":"2019","journal-title":"Curr Protoc in Microbiol"},{"key":"ppat.1011763.ref042","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1534\/genetics.118.300996","article-title":"A high-resolution map of meiotic recombination in Cryptococcus deneoformans demonstrates decreased recombination in unisexual reproduction","volume":"209","author":"C Roth","year":"2018","journal-title":"Genetics"},{"key":"ppat.1011763.ref043","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pgen.1009313","article-title":"Pleiotropy and epistasis within and between signaling pathways defines the genetic architecture of fungal virulence","volume":"17","author":"C Roth","year":"2021","journal-title":"PLoS Genetics"},{"key":"ppat.1011763.ref044","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1093\/genetics\/143.2.1013","article-title":"Confidence intervals in QTL mapping by bootstrapping","volume":"143","author":"PM Visscher","year":"1996","journal-title":"Genetics"},{"key":"ppat.1011763.ref045","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1093\/genetics\/138.3.963","article-title":"Empirical threshold values for quantitative trait mapping","volume":"138","author":"GA Churchill","year":"1994","journal-title":"Genetics"},{"key":"ppat.1011763.ref046","first-page":"118323","article-title":"Population Genomics 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Haplotype-based variant detection from short-read sequencing. arXiv:1207.3907v2."},{"issue":"12","key":"ppat.1011763.ref050","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1093\/bioinformatics\/btaa1016","article-title":"Liftoff: accurate mapping of gene annotations","volume":"37","author":"A Shumate","year":"2021","journal-title":"Bioinformatics"},{"key":"ppat.1011763.ref051","first-page":"1","article-title":"Systematic functional profiling of transcription factor networks in Cryptococcus neoformans","volume":"6","author":"KW Jung","year":"2015","journal-title":"Nat Commun"},{"issue":"12","key":"ppat.1011763.ref052","doi-asserted-by":"crossref","first-page":"e3001007","DOI":"10.1371\/journal.pbio.3001007","article-title":"ClipKIT: A multiple sequence alignment trimming software for accurate phylogenomic inference","volume":"18","author":"JL Steenwyk","year":"2020","journal-title":"PLoS Biol"},{"issue":"12","key":"ppat.1011763.ref053","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1093\/bioinformatics\/btq228","article-title":"DendroPy: a Python library for phylogenetic computing","volume":"26","author":"J Sukumaran","year":"2010","journal-title":"Bioinformatics"},{"key":"ppat.1011763.ref054","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/nbt.3519","article-title":"Near-optimal probabilistic RNA-seq quantification","volume":"34","author":"NL Bray","year":"2016","journal-title":"Nature Biotech"},{"key":"ppat.1011763.ref055","article-title":"XSTREME: Comprehensive motif analysis of biological sequence datasets","author":"CE Grant","year":"2021","journal-title":"bioRxiv"},{"issue":"W1","key":"ppat.1011763.ref056","doi-asserted-by":"crossref","first-page":"W39","DOI":"10.1093\/nar\/gkv416","article-title":"The MEME Suite","volume":"43","author":"TL Bailey","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"ppat.1011763.ref057","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1093\/mmy\/myv012","article-title":"Morphology and its underlying genetic regulation impact the interaction between Cryptococcus neoformans and its hosts","volume":"53","author":"J Lin","year":"2015","journal-title":"Med Mycol"},{"key":"ppat.1011763.ref058","first-page":"177","article-title":"Chronic cryptococcal meningitis. A new experimental model in rabbits","volume":"101","author":"JR Perfect","year":"1980","journal-title":"Am J Pathol"},{"key":"ppat.1011763.ref059","doi-asserted-by":"crossref","first-page":"4831","DOI":"10.1128\/IAI.71.9.4831-4841.2003","article-title":"Sexual cycle of Cryptococcus neoformans var. grubii and virulence of congenic a and \u03b1 isolates","volume":"71","author":"K Nielsen","year":"2003","journal-title":"Infect Immun"},{"key":"ppat.1011763.ref060","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1128\/EC.2.6.1162-1168.2003","article-title":"Evidence of sexual recombination among Cryptococcus neoformans serotype A isolates in sub-Saharan Africa","volume":"2","author":"AP Litvintseva","year":"2003","journal-title":"Eukaryot Cell"},{"key":"ppat.1011763.ref061","doi-asserted-by":"crossref","first-page":"3559","DOI":"10.1111\/mec.13260","article-title":"Comparative analyses of clinical and environmental populations of Cryptococcus neoformans in 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replication of a resistin mRNA QTL, but not QTLs for circulating levels of resistin, in human and baboon","volume":"101","author":"ME Tejero","year":"2008","journal-title":"Heredity"},{"issue":"40","key":"ppat.1011763.ref079","doi-asserted-by":"crossref","first-page":"e2212199119","DOI":"10.1073\/pnas.2212199119","article-title":"Leveraging orthology within maize and Arabidopsis QTL to identify genes affecting natural variation in gravitropism","volume":"119","author":"T Yoshihara","year":"2022","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5","key":"ppat.1011763.ref080","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1534\/g3.113.009142","article-title":"Yeast growth plasticity is regulated by environment-specific multi-QTL interactions","volume":"4","author":"A Bhatia","year":"2014","journal-title":"G3 (Bethesda)"},{"key":"ppat.1011763.ref081","article-title":"Barcoded Bulk QTL mapping reveals highly polygenic and epistatic architecture of complex traits in yeast","volume":"11","author":"ANN Ba","year":"2022","journal-title":"eLife"},{"issue":"8","key":"ppat.1011763.ref082","doi-asserted-by":"crossref","first-page":"e2122293119","DOI":"10.1073\/pnas.2122293119","article-title":"Epistatic genetic interactions govern morphogenesis during sexual reproduction and infection in a global human fungal pathogen","volume":"119","author":"S Sun","year":"2022","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ppat.1011763.ref083","doi-asserted-by":"crossref","first-page":"3131","DOI":"10.1128\/iai.63.8.3131-3136.1995","article-title":"Cryptococcus neoformans melanin and virulence: Mechanism of action","volume":"63","author":"Y Wang","year":"1995","journal-title":"Infect Immun"},{"issue":"7","key":"ppat.1011763.ref084","doi-asserted-by":"crossref","first-page":"3004","DOI":"10.1128\/iai.62.7.3004-3007.1994","article-title":"Susceptibility of melanized and nonmelanized Cryptococcus neoformans to nitrogen- and oxygen-derived oxidants","volume":"62","author":"Y Wang","year":"1994","journal-title":"Infect Immun"},{"key":"ppat.1011763.ref085","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.femsyr.2004.04.004","article-title":"Role of laccase in the biology and virulence of Cryptococcus neoformans","volume":"5","author":"X Zhu","year":"2004","journal-title":"FEMS Yeast Research"},{"issue":"12","key":"ppat.1011763.ref086","doi-asserted-by":"crossref","first-page":"R125","DOI":"10.1186\/gb-2011-12-12-r125","article-title":"Curated collection of yeast transcription factor DNA binding specificity data reveals novel structural and gene regulatory insights","volume":"12","author":"R Gord\u00e2n","year":"2011","journal-title":"Genome Biol"},{"issue":"45","key":"ppat.1011763.ref087","doi-asserted-by":"crossref","first-page":"E3084","DOI":"10.1073\/pnas.1212457109","article-title":"Basic leucine zipper transcription factor Hac1 binds DNA in two distinct modes as revealed by microfluidic analyses","volume":"109","author":"PM Fordyce","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"3","key":"ppat.1011763.ref088","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1128\/EC.00213-06","article-title":"Divergence of protein kinase A catalytic subunits in Cryptococcus neoformans and Cryptococcus gattii illustrates evolutionary reconfiguration of a signaling cascade","volume":"6","author":"JK Hicks","year":"2007","journal-title":"Eukaryot Cell"},{"issue":"5977","key":"ppat.1011763.ref089","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1126\/science.1189015","article-title":"Genotype to phenotype: a complex problem","volume":"328","author":"RD Dowell","year":"2010","journal-title":"Science"},{"issue":"11","key":"ppat.1011763.ref090","doi-asserted-by":"crossref","first-page":"5045","DOI":"10.1073\/pnas.1820915116","article-title":"Complex modifier landscape underlying genetic background effects","volume":"116","author":"J 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