{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T00:16:20Z","timestamp":1790381780518,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1009832","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,4,18]],"date-time":"2022-04-18T00:00:00Z","timestamp":1650240000000}}],"reference-count":51,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T00:00:00Z","timestamp":1649203200000},"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","doi-asserted-by":"publisher","award":["R01AI137418 and 1U19AI166059"],"award-info":[{"award-number":["R01AI137418 and 1U19AI166059"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"national institute of allergy and infectious diseases","doi-asserted-by":"publisher","award":["2R37AI066224"],"award-info":[{"award-number":["2R37AI066224"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"national institute of allergy and infectious diseases","doi-asserted-by":"publisher","award":["5R01AI146584"],"award-info":[{"award-number":["5R01AI146584"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["VFR-19-633952"],"award-info":[{"award-number":["VFR-19-633952"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"national institute of allergy and infectious diseases","doi-asserted-by":"publisher","award":["R21AI144855"],"award-info":[{"award-number":["R21AI144855"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"national institute of allergy and infectious diseases","doi-asserted-by":"publisher","award":["MRP-17-454959 and 1U19AI166798"],"award-info":[{"award-number":["MRP-17-454959 and 1U19AI166798"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"national institute of allergy and infectious diseases","doi-asserted-by":"publisher","award":["U54AI65359"],"award-info":[{"award-number":["U54AI65359"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"national institute of allergy and infectious diseases","doi-asserted-by":"publisher","award":["1R01AI132140"],"award-info":[{"award-number":["1R01AI132140"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"national institute of allergy and infectious diseases","doi-asserted-by":"publisher","award":["1U01AI122275"],"award-info":[{"award-number":["1U01AI122275"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    <jats:italic>Coccidioides<\/jats:italic>\n                    spp. are mammalian fungal pathogens endemic to the Southwestern US and other desert regions of Mexico, Central and South America, with the bulk of US infections occurring in California and Arizona. In the soil,\n                    <jats:italic>Coccidioides<\/jats:italic>\n                    grows in a hyphal form that differentiates into 3\u20135 micron asexual spores (arthroconidia). When arthroconidia are inhaled by mammals they undergo a unique developmental transition from polar hyphal growth to isotropic expansion with multiple rounds of nuclear division, prior to segmentation, forming large spherules filled with endospores. Very little is understood about the molecular basis of spherule formation. Here we characterize the role of the conserved transcription factor Ryp1 in\n                    <jats:italic>Coccidioides<\/jats:italic>\n                    development. We show that\n                    <jats:italic>Coccidioides<\/jats:italic>\n                    \u0394\n                    <jats:italic>ryp1<\/jats:italic>\n                    mutants have altered colony morphology under hypha-promoting conditions and are unable to form mature spherules under spherule-promoting conditions. We analyze the transcriptional profile of wild-type and \u0394\n                    <jats:italic>ryp1<\/jats:italic>\n                    mutant cells under hypha- and spherule-promoting conditions, thereby defining a set of hypha- or spherule-enriched transcripts (\u201cmorphology-regulated\u201d genes) that are dependent on Ryp1 for their expression. Forty percent of morphology-regulated expression is Ryp1-dependent, indicating that Ryp1 plays a dual role in both hyphal and spherule development. Ryp1-dependent transcripts include key virulence factors such as SOWgp, which encodes the spherule outer wall glycoprotein. Concordant with its role in spherule development, we find that the \u0394\n                    <jats:italic>ryp1<\/jats:italic>\n                    mutant is completely avirulent in the mouse model of coccidioidomycosis, indicating that Ryp1-dependent pathways are essential for the ability of\n                    <jats:italic>Coccidioides<\/jats:italic>\n                    to cause disease. Vaccination of C57BL\/6 mice with live \u0394\n                    <jats:italic>ryp1<\/jats:italic>\n                    spores does not provide any protection from lethal\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>posadasii<\/jats:italic>\n                    intranasal infection, consistent with our findings that the \u0394\n                    <jats:italic>ryp1<\/jats:italic>\n                    mutant fails to make mature spherules and likely does not express key antigens required for effective vaccination. Taken together, this work identifies the first transcription factor that drives mature spherulation and virulence in\n                    <jats:italic>Coccidioides<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1009832","type":"journal-article","created":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T13:55:24Z","timestamp":1649253324000},"page":"e1009832","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":28,"title":["The WOPR family protein Ryp1 is a key regulator of gene expression, development, and virulence in the thermally dimorphic fungal pathogen Coccidioides posadasii"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7620-3862","authenticated-orcid":true,"given":"M. Alejandra","family":"Mandel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sinem","family":"Beyhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8815-7384","authenticated-orcid":true,"given":"Mark","family":"Voorhies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1011-0708","authenticated-orcid":true,"given":"Lisa F.","family":"Shubitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John N.","family":"Galgiani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7714-1352","authenticated-orcid":true,"given":"Marc J.","family":"Orbach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3987-7534","authenticated-orcid":true,"given":"Anita","family":"Sil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,4,6]]},"reference":[{"key":"ppat.1009832.ref001","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.micinf.2014.06.011","article-title":"Valley fever: danger lurking in a dust cloud","volume":"16","author":"L Johnson","year":"2014","journal-title":"Microbes Infect"},{"key":"ppat.1009832.ref002","first-page":"217","article-title":"Increase in reported coccidioidomycosis\u2014United States, 1998\u20132011","volume":"62","author":"Centers for Disease Control and Prevention (CDC)","year":"2013","journal-title":"MMWR Morb Mortal Wkly 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