{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:52:04Z","timestamp":1787028724402,"version":"build-2736575974"},"reference-count":90,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,11,26]],"date-time":"2021-11-26T00:00:00Z","timestamp":1637884800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["2017\/04592-0"],"award-info":[{"award-number":["2017\/04592-0"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"National Council for Scientific and Technological Development","doi-asserted-by":"publisher","award":["141726\/2017-2"],"award-info":[{"award-number":["141726\/2017-2"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"National Council for Scientific and Technological Development","doi-asserted-by":"publisher","award":["311008\/2020-8"],"award-info":[{"award-number":["311008\/2020-8"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>Dimorphic fungi of the Paracoccidioides genus are the causative agents of paracoccidioidomycosis (PCM), an endemic disease in Latin America with a high incidence in Brazil. This pathogen presents as infective mycelium at 25 \u00b0C in the soil, reverting to its pathogenic form when inhaled by the mammalian host (37 \u00b0C). Among these dimorphic fungal species, dimorphism regulating histidine kinase (Drk1) plays an essential role in the morphological transition. These kinases are present in bacteria and fungi but absent in mammalian cells and are important virulence and cellular survival regulators. Hence, the purpose of this study was to investigate the role of PbDrk1 in the cell wall modulation of P. brasiliensis. We observed that PbDrk1 participates in fungal resistance to different cell wall-disturbing agents by reducing viability after treatment with iDrk1. To verify the role of PbDRK1 in cell wall morphogenesis, qPCR results showed that samples previously exposed to iDrk1 presented higher expression levels of several genes related to cell wall modulation. One of them was FKS1, a \u03b2-glucan synthase that showed a 3.6-fold increase. Furthermore, confocal microscopy analysis and flow cytometry showed higher \u03b2-glucan exposure on the cell surface of P. brasiliensis after incubation with iDrk1. Accordingly, through phagocytosis assays, a significantly higher phagocytic index was observed in yeasts treated with iDrk1 than the control group, demonstrating the role of PbDrk1 in cell wall modulation, which then becomes a relevant target to be investigated. In parallel, the immune response profile showed increased levels of proinflammatory cytokines. Finally, our data strongly suggest that PbDrk1 modulates cell wall component expression, among which we can identify \u03b2-glucan. Understanding this signalling pathway may be of great value for identifying targets of antifungal molecular activity since HKs are not present in mammals.<\/jats:p>","DOI":"10.3390\/jof7121014","type":"journal-article","created":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T01:43:22Z","timestamp":1638323002000},"page":"1014","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The Role of Dimorphism Regulating Histidine Kinase (Drk1) in the Pathogenic Fungus Paracoccidioides brasiliensis Cell Wall"],"prefix":"10.3390","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1586-7005","authenticated-orcid":false,"given":"Marina Valente","family":"Navarro","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology and Parasitology, Federal University of S\u00e3o Paulo, S\u00e3o Paulo 04023-062, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmin Nascimento","family":"de Barros","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Federal University of S\u00e3o Paulo, Diadema 09913-030, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilson Dias","family":"Segura","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Federal University of S\u00e3o Paulo, Diadema 09913-030, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6017-6671","authenticated-orcid":false,"given":"Alison Felipe Alencar","family":"Chaves","sequence":"additional","affiliation":[{"name":"Center of Toxins, Immune-Response and Cell Signaling\u2014CeTICS, Instituto Butantan, S\u00e3o Paulo 05503-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grasielle Pereira","family":"Jannuzzi","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analyses, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen Spadari","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Federal University of S\u00e3o Paulo, Diadema 09913-030, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patr\u00edcia","family":"Xander","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Federal University of S\u00e3o Paulo, Diadema 09913-030, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0280-6828","authenticated-orcid":false,"given":"Wagner Luiz","family":"Batista","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Parasitology, Federal University of S\u00e3o Paulo, S\u00e3o Paulo 04023-062, Brazil"},{"name":"Department of Pharmaceutical Sciences, Federal University of S\u00e3o Paulo, Diadema 09913-030, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,26]]},"reference":[{"key":"ref_1","first-page":"e0500001","article-title":"II Consenso Brasileiro em Paracoccidioidomicose-2017","volume":"27","author":"Mendes","year":"2018","journal-title":"Epidemiol. 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