{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T06:43:14Z","timestamp":1791873794945,"version":"4.3.4"},"update-to":[{"DOI":"10.1371\/journal.ppat.1010321","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,8,30]],"date-time":"2022-08-30T00:00:00Z","timestamp":1661817600000}}],"reference-count":51,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2022,8,15]],"date-time":"2022-08-15T00:00:00Z","timestamp":1660521600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/R008485\/1"],"award-info":[{"award-number":["BB\/R008485\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/M014525\/1"],"award-info":[{"award-number":["BB\/M014525\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["211241\/Z\/18\/Z"],"award-info":[{"award-number":["211241\/Z\/18\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000288","name":"Royal Society","doi-asserted-by":"publisher","award":["211241\/Z\/18\/Z"],"award-info":[{"award-number":["211241\/Z\/18\/Z"]}],"id":[{"id":"10.13039\/501100000288","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003971","name":"Islamic Development Bank","doi-asserted-by":"crossref","award":["PhD scholarship"],"award-info":[{"award-number":["PhD scholarship"]}],"id":[{"id":"10.13039\/501100003971","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Cryptococcosis is a potentially lethal fungal infection of humans caused by organisms within the\n                    <jats:italic>Cryptococcus neoformans\/gattii<\/jats:italic>\n                    species complex. Whilst\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>neoformans<\/jats:italic>\n                    is a relatively common pathogen of immunocompromised individuals,\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>gattii<\/jats:italic>\n                    is capable of acting as a primary pathogen of immunocompetent individuals. Within the host, both species undergo morphogenesis to form titan cells: exceptionally large cells that are critical for disease establishment. To date, the induction, defining attributes, and underlying mechanism of titanisation have been mainly characterized in\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>neoformans<\/jats:italic>\n                    . Here, we report the serendipitous discovery of a simple and robust protocol for\n                    <jats:italic>in vitro<\/jats:italic>\n                    induction of titan cells in\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>gattii<\/jats:italic>\n                    . Using this\n                    <jats:italic>in vitro<\/jats:italic>\n                    approach, we reveal a remarkably high capacity for titanisation within\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>gattii<\/jats:italic>\n                    , especially in strains associated with the Pacific Northwest Outbreak, and characterise strain-specific differences within the clade. In particular, this approach demonstrates for the first time that cell size changes, DNA amplification, and budding are not always synchronous during titanisation. Interestingly, however, exhibition of these cell cycle phenotypes was correlated with genes associated with cell cycle progression including\n                    <jats:italic>CDC11<\/jats:italic>\n                    ,\n                    <jats:italic>CLN1<\/jats:italic>\n                    ,\n                    <jats:italic>BUB2<\/jats:italic>\n                    , and\n                    <jats:italic>MCM6<\/jats:italic>\n                    . Finally, our findings reveal exogenous p-Aminobenzoic acid to be a key inducer of titanisation in this organism. Consequently, this approach offers significant opportunities for future exploration of the underlying mechanism of titanisation in this genus.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1010321","type":"journal-article","created":{"date-parts":[[2022,8,15]],"date-time":"2022-08-15T13:43:38Z","timestamp":1660571018000},"page":"e1010321","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":20,"title":["An in vitro method for inducing titan cells reveals novel features of yeast-to-titan switching in the human fungal pathogen Cryptococcus gattii"],"prefix":"10.1371","volume":"18","author":[{"given":"Lamin","family":"Saidykhan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joao","family":"Correia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrey","family":"Romanyuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna F. A.","family":"Peacock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume E.","family":"Desanti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leanne","family":"Taylor-Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Makarova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth R.","family":"Ballou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5364-1838","authenticated-orcid":true,"given":"Robin C.","family":"May","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,8,15]]},"reference":[{"key":"ppat.1010321.ref001","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/nrmicro.2015.6","article-title":"Cryptococcus: from environmental saprophyte to global pathogen","volume":"14","author":"RC May","year":"2016","journal-title":"Nat Rev Microbiol"},{"key":"ppat.1010321.ref002","doi-asserted-by":"crossref","first-page":"fov106","DOI":"10.1093\/femsyr\/fov106","article-title":"What makes Cryptococcus gattii a pathogen?","volume":"16","author":"E Bielska","year":"2016","journal-title":"FEMS Yeast Res"},{"key":"ppat.1010321.ref003","doi-asserted-by":"crossref","first-page":"a019760","DOI":"10.1101\/cshperspect.a019760","article-title":"Cryptococcus neoformans and Cryptococcus gattii, the etiologic agents of cryptococcosis","volume":"4","author":"KJ Kwon-Chung","year":"2014","journal-title":"Cold Spring Harb Perspect Med"},{"key":"ppat.1010321.ref004","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/j.mib.2008.09.018","article-title":"Fungal adaptation to the mammalian host: it is a new world, after all","volume":"11","author":"NM Cooney","year":"2008","journal-title":"Curr Opin Microbiol"},{"key":"ppat.1010321.ref005","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.mib.2017.10.012","article-title":"The cause and effect of Cryptococcus interactions with the host","volume":"40","author":"ER Ballou","year":"2017","journal-title":"Curr Opin Microbiol"},{"key":"ppat.1010321.ref006","doi-asserted-by":"crossref","first-page":"e1000953","DOI":"10.1371\/journal.ppat.1000953","article-title":"Cryptococcal cell morphology affects host cell interactions and pathogenicity","volume":"6","author":"LH Okagaki","year":"2010","journal-title":"PLoS Pathog"},{"key":"ppat.1010321.ref007","doi-asserted-by":"crossref","first-page":"e1000945","DOI":"10.1371\/journal.ppat.1000945","article-title":"Fungal cell gigantism during mammalian infection","volume":"6","author":"O Zaragoza","year":"2010","journal-title":"PLoS Pathog"},{"key":"ppat.1010321.ref008","doi-asserted-by":"crossref","first-page":"2355","DOI":"10.1099\/00221287-147-8-2355","article-title":"Dynamic changes in the morphology of Cryptococcus neoformans during murine pulmonary infection","volume":"147","author":"M Feldmesser","year":"2001","journal-title":"Microbiology"},{"key":"ppat.1010321.ref009","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1128\/EC.00121-12","article-title":"Titan cells confer protection from phagocytosis in Cryptococcus neoformans infections","volume":"11","author":"LH Okagaki","year":"2012","journal-title":"Eukaryot Cell"},{"key":"ppat.1010321.ref010","doi-asserted-by":"crossref","first-page":"3776","DOI":"10.1128\/IAI.00507-12","article-title":"Titan cell production enhances the virulence of Cryptococcus neoformans","volume":"80","author":"JN Crabtree","year":"2012","journal-title":"Infect Immun"},{"key":"ppat.1010321.ref011","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1128\/am.25.2.309-312.1973","article-title":"Cryptococcus neoformans of unusual morphology","volume":"25","author":"JG Cruickshank","year":"1973","journal-title":"Appl Microbiol"},{"key":"ppat.1010321.ref012","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1128\/jcm.22.6.1068-1070.1985","article-title":"Large Cryptococcus neoformans isolated from brain abscess","volume":"22","author":"GL Love","year":"1985","journal-title":"J Clin Microbiol"},{"key":"ppat.1010321.ref013","doi-asserted-by":"crossref","first-page":"e1006978","DOI":"10.1371\/journal.ppat.1006978","article-title":"The Cryptococcus neoformans Titan cell is an inducible and regulated morphotype underlying pathogenesis","volume":"14","author":"IM Dambuza","year":"2018","journal-title":"PLoS Pathog"},{"key":"ppat.1010321.ref014","doi-asserted-by":"crossref","first-page":"e1007007","DOI":"10.1371\/journal.ppat.1007007","article-title":"Cryptococcus neoformans can form titan-like cells in vitro in response to multiple signals","volume":"14","author":"N Trevijano-Contador","year":"2018","journal-title":"PLoS Pathog"},{"key":"ppat.1010321.ref015","doi-asserted-by":"crossref","first-page":"e1006982","DOI":"10.1371\/journal.ppat.1006982","article-title":"Titan cells formation in Cryptococcus neoformans is finely tuned by environmental conditions and modulated by positive and negative genetic regulators","volume":"14","author":"B Hommel","year":"2018","journal-title":"PLoS Pathog"},{"key":"ppat.1010321.ref016","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1007\/s40588-018-0107-9","article-title":"The Cryptococcus neoformans Titan Cell: From In Vivo Phenomenon to In Vitro Model","volume":"5","author":"X Zhou","year":"2018","journal-title":"Curr Clin Microbiol Rep"},{"key":"ppat.1010321.ref017","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1128\/EC.00109-14","article-title":"A Ric8\/synembryn homolog promotes Gpa1 and Gpa2 activation to respectively regulate cyclic AMP and pheromone signaling in Cryptococcus neoformans","volume":"13","author":"J Gong","year":"2014","journal-title":"Eukaryot Cell"},{"key":"ppat.1010321.ref018","doi-asserted-by":"crossref","first-page":"e0250921","DOI":"10.1128\/mBio.02509-21","article-title":"The Cyclin Cln1 Controls Polyploid Titan Cell Formation following a Stress-Induced G2 Arrest in Cryptococcus","volume":"12","author":"S Altamirano","year":"2021","journal-title":"mBio"},{"key":"ppat.1010321.ref019","doi-asserted-by":"crossref","first-page":"e24485","DOI":"10.1371\/journal.pone.0024485","article-title":"Cryptococcus neoformans capsular enlargement and cellular gigantism during Galleria mellonella infection","volume":"6","author":"R Garc\u00eda-Rodas","year":"2011","journal-title":"PLoS One"},{"issue":"6","key":"ppat.1010321.ref020","doi-asserted-by":"crossref","first-page":"e00350","DOI":"10.1128\/mSphere.00350-16","article-title":"Species in the Cryptococcus gattii Complex Differ in Capsule and Cell Size following Growth under Capsule-Inducing Conditions","volume":"1","author":"KE Fernandes","year":"2016","journal-title":"mSphere"},{"issue":"5","key":"ppat.1010321.ref021","doi-asserted-by":"crossref","first-page":"e02016","DOI":"10.1128\/mBio.02016-18","article-title":"Phenotypic Variability Correlates with Clinical Outcome in Cryptococcus Isolates Obtained from Botswanan HIV\/AIDS Patients","volume":"9","author":"KE Fernandes","year":"2018","journal-title":"mBio"},{"issue":"2","key":"ppat.1010321.ref022","first-page":"e03457","article-title":"The Transcription Factor Pdr802 Regulates Titan Cell Formation and Pathogenicity of Cryptococcus neoformans","volume":"12","author":"JCV Reuwsaat","year":"2021","journal-title":"mBio"},{"key":"ppat.1010321.ref023","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1128\/EC.05179-11","article-title":"Cryptococcal titan cell formation is regulated by G-protein signaling in response to multiple stimuli","volume":"10","author":"LH Okagaki","year":"2011","journal-title":"Eukaryot Cell"},{"issue":"5","key":"ppat.1010321.ref024","doi-asserted-by":"crossref","first-page":"01340","DOI":"10.1128\/mBio.01340-15","article-title":"Polyploid Titan Cells Produce Haploid and Aneuploid Progeny To Promote Stress Adaptation","volume":"6","author":"AC Gerstein","year":"2015","journal-title":"MBio"},{"key":"ppat.1010321.ref025","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.tcsw.2017.12.001","article-title":"Titan cell production in Cryptococcus neoformans reshapes the cell wall and capsule composition during infection","volume":"1","author":"L Mukaremera","year":"2018","journal-title":"Cell Surf"},{"key":"ppat.1010321.ref026","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.mib.2013.03.006","article-title":"Titan cells in Cryptococcus neoformans: cells with a giant impact","volume":"16","author":"O Zaragoza","year":"2013","journal-title":"Curr Opin Microbiol"},{"key":"ppat.1010321.ref027","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1251\/bpo68","article-title":"Experimental modulation of capsule size in Cryptococcus neoformans","volume":"6","author":"O Zaragoza","year":"2004","journal-title":"Biol Proced Online"},{"key":"ppat.1010321.ref028","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1128\/EC.5.1.103-111.2006","article-title":"Cryptococcus neoformans senses CO2 through the carbonic anhydrase Can2 and the adenylyl cyclase Cac1","volume":"5","author":"EG Mogensen","year":"2006","journal-title":"Eukaryot Cell"},{"key":"ppat.1010321.ref029","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1016\/j.cub.2005.09.047","article-title":"Carbonic anhydrase and CO2 sensing during Cryptococcus neoformans growth, differentiation, and virulence","volume":"15","author":"YS Bahn","year":"2005","journal-title":"Curr Biol"},{"key":"ppat.1010321.ref030","doi-asserted-by":"crossref","first-page":"6076","DOI":"10.1128\/IAI.67.11.6076-6083.1999","article-title":"Phenotypic switching in Cryptococcus neoformans results in changes in cellular morphology and glucuronoxylomannan structure","volume":"67","author":"BC Fries","year":"1999","journal-title":"Infect Immun"},{"key":"ppat.1010321.ref031","doi-asserted-by":"crossref","first-page":"e368","DOI":"10.1371\/journal.pone.0000368","article-title":"The temperature-sensitive role of Cryptococcus neoformans ROM2 in cell morphogenesis","volume":"2","author":"BB Fuchs","year":"2007","journal-title":"PLoS One"},{"key":"ppat.1010321.ref032","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.fgb.2015.02.009","article-title":"Recognition of seven species in the Cryptococcus gattii\/Cryptococcus neoformans species complex","volume":"78","author":"F Hagen","year":"2015","journal-title":"Fungal Genet Biol"},{"key":"ppat.1010321.ref033","first-page":"e1003771","article-title":"Transmission of Hypervirulence Traits via Sexual Reproduction within and between Lineages of the Human Fungal Pathogen Cryptococcus gattii","author":"K Voelz","year":"2013","journal-title":"PLOS Pathog"},{"key":"ppat.1010321.ref034","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1128\/EC.05273-11","article-title":"Adaptation of Cryptococcus neoformans to mammalian hosts: integrated regulation of metabolism and virulence","volume":"11","author":"J Kronstad","year":"2012","journal-title":"Eukaryot Cell"},{"key":"ppat.1010321.ref035","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1172\/JCI13407","article-title":"Phenotypic switching of Cryptococcus neoformans occurs in vivo and influences the outcome of infection","volume":"108","author":"BC Fries","year":"2001","journal-title":"J Clin Invest"},{"issue":"4","key":"ppat.1010321.ref036","doi-asserted-by":"crossref","first-page":"66","DOI":"10.3390\/jof3040066","article-title":"Morphology Changes in Human Fungal Pathogens upon Interaction with the Host","volume":"3","author":"Z Li","year":"2017","journal-title":"J Fungi (Basel)"},{"issue":"6","key":"ppat.1010321.ref037","doi-asserted-by":"crossref","first-page":"e01375","DOI":"10.1128\/mBio.01375-18","article-title":"Maintenance of Mitochondrial Morphology in Cryptococcus neoformans Is Critical for Stress Resistance and Virulence","volume":"9","author":"AL Chang","year":"2018","journal-title":"mBio"},{"key":"ppat.1010321.ref038","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1128\/CMR.00001-12","article-title":"The Cryptococcus neoformans capsule: a sword and a shield","volume":"25","author":"TR O\u2019Meara","year":"2012","journal-title":"Clin Microbiol Rev"},{"key":"ppat.1010321.ref039","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1083\/jcb.75.2.422","article-title":"Unequal division in Saccharomyces cerevisiae and its implications for the control of cell division","volume":"75","author":"LH Hartwell","year":"1977","journal-title":"J Cell Biol"},{"key":"ppat.1010321.ref040","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1126\/science.183.4120.46","article-title":"Genetic control of the cell division cycle in yeast","volume":"183","author":"LH Hartwell","year":"1974","journal-title":"Science"},{"key":"ppat.1010321.ref041","first-page":"231","article-title":"Unbudded G2 as well as G1 arrest in the stationary phase of the basidiomycetous yeast Cryptococcus neoformans","volume":"129","author":"K Takeo","year":"1995","journal-title":"FEMS Microbiol Lett"},{"key":"ppat.1010321.ref042","doi-asserted-by":"crossref","first-page":"213025","DOI":"10.1242\/jcs.213025","article-title":"The cell biology of quiescent yeast\u2014a diversity of individual scenarios","volume":"132","author":"I Sagot","year":"2019","journal-title":"J Cell Sci"},{"key":"ppat.1010321.ref043","doi-asserted-by":"crossref","first-page":"e00103","DOI":"10.1128\/mBio.00103-12","article-title":"The primary target organ of Cryptococcus gattii is different from that of Cryptococcus neoformans in a murine model","volume":"3","author":"P Ngamskulrungroj","year":"2012","journal-title":"MBio"},{"key":"ppat.1010321.ref044","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/j.chom.2016.05.001","article-title":"Intracellular Action of a Secreted Peptide Required for Fungal Virulence","volume":"19","author":"CM Homer","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ppat.1010321.ref045","doi-asserted-by":"crossref","first-page":"e00986","DOI":"10.1128\/mBio.00986-13","article-title":"Quorum sensing-mediated, cell density-dependent regulation of growth and virulence in Cryptococcus neoformans","volume":"5","author":"P Albuquerque","year":"2014","journal-title":"mBio"},{"key":"ppat.1010321.ref046","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1021\/acs.jafc.7b05084","article-title":"Production of Antifungal p-Aminobenzoic Acid in Lysobacter antibioticus OH13","volume":"66","author":"P Laborda","year":"2018","journal-title":"J Agric Food Chem"},{"key":"ppat.1010321.ref047","doi-asserted-by":"crossref","first-page":"2157","DOI":"10.1021\/acs.jafc.8b05618","article-title":"Antifungal Metabolite p-Aminobenzoic Acid (pABA): Mechanism of Action and Efficacy for the Biocontrol of Pear Bitter Rot Disease","volume":"67","author":"P Laborda","year":"2019","journal-title":"J Agric Food Chem"},{"key":"ppat.1010321.ref048","doi-asserted-by":"crossref","first-page":"e91298","DOI":"10.1371\/journal.pone.0091298","article-title":"Para-aminobenzoic acid (PABA) synthase enhances thermotolerance of mushroom Agaricus bisporus","volume":"9","author":"Z Lu","year":"2014","journal-title":"PLoS One"},{"key":"ppat.1010321.ref049","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1111\/cmi.12394","article-title":"The fungal pathogen Cryptococcus neoformans manipulates macrophage phagosome maturation","volume":"17","author":"LM Smith","year":"2015","journal-title":"Cell Microbiol"},{"key":"ppat.1010321.ref050","doi-asserted-by":"crossref","first-page":"e0153356","DOI":"10.1371\/journal.pone.0153356","article-title":"In Vitro Analysis of Metabolites Secreted during Infection of Lung Epithelial Cells by Cryptococcus neoformans","volume":"11","author":"KL Liew","year":"2016","journal-title":"PLoS One"},{"key":"ppat.1010321.ref051","first-page":"56957","article-title":"Automated Measurement of Cryptococcal Species Polysaccharide Capsule and Cell Body","volume":"131","author":"Q Dragotakes","year":"2018","journal-title":"J Vis Exp"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1010321","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,8,30]],"date-time":"2022-08-30T00:00:00Z","timestamp":1661817600000}},{"DOI":"10.1371\/journal.ppat.1011001","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2022,11,29]],"date-time":"2022-11-29T00:00:00Z","timestamp":1669680000000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1010321","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,30]],"date-time":"2022-08-30T14:43:27Z","timestamp":1661870607000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1010321"}},"subtitle":[],"editor":[{"given":"Kirsten","family":"Nielsen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,8,15]]},"references-count":51,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,8,15]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1010321","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2022.02.01.478613","asserted-by":"object"}]},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,15]]}}}