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The infection begins after inhalation of the fungal propagules and their thermo-dimorphic shift to yeast form. Proteases play an important role in the host invasion process and immune modulation in many pathogenic microorganisms. Aspartyl proteases are virulence factors in many human fungal pathogens that play an important role in the host invasion process morphogenesis, cellular function, immunity, and nutrition. In the present study, we characterized the modulation of acid proteases from Paracoccidioides brasiliensis. We detected four aspartyl proteases in P. brasiliensis with high homology to aspartic protease from Saccharomyces cerevisiae Pep4. Furthermore, we demonstrated that Pepstatin A can inhibit dimorphic switching (mycelium\u2192yeast) in P. brasiliensis. In addition, these genes were modulated during thermo-dimorphism (M\u2192Y transition) in the presence or absence of carbon and nitrogen sources and during growth at pH 4 during 24 and 48 h. We also observed that P. brasiliensis increase the secretion of aspartic proteases when cultivated at pH 4, and these acid proteases cleave BSA, collagen, and hemoglobin. These data suggest that aspartyl proteases are modulated by environmental conditions and during fungal thermo-dimorphism. Thus, this work brings new possibilities for studying the role of aspartyl proteases in the host\u2013pathogen relationship and P. brasiliensis biology.<\/jats:p>","DOI":"10.3390\/jof9030375","type":"journal-article","created":{"date-parts":[[2023,3,20]],"date-time":"2023-03-20T03:30:31Z","timestamp":1679283031000},"page":"375","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Characterization of Aspartic Proteases from Paracoccidioides brasiliensis and Their Role in Fungal Thermo-Dimorphism"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4002-0634","authenticated-orcid":false,"given":"Rafael de Souza","family":"Silva","sequence":"first","affiliation":[{"name":"Departamento Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo 04023-062, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilson Dias","family":"Segura","sequence":"additional","affiliation":[{"name":"Departamento Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo 04023-062, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2420-1563","authenticated-orcid":false,"given":"Reinaldo Souza","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Departamento de Ci\u00eancias Farmac\u00eauticas, Instituto de Ci\u00eancias Ambientais, Qu\u00edmicas e Farmac\u00eauticas, Universidade Federal de S\u00e3o Paulo, Diadema 09913-030, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Xander","sequence":"additional","affiliation":[{"name":"Departamento de Ci\u00eancias Farmac\u00eauticas, Instituto de Ci\u00eancias Ambientais, Qu\u00edmicas e Farmac\u00eauticas, Universidade Federal de S\u00e3o Paulo, Diadema 09913-030, SP, 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":"Departamento Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo 04023-062, SP, Brazil"},{"name":"Departamento de Ci\u00eancias Farmac\u00eauticas, Instituto de Ci\u00eancias Ambientais, Qu\u00edmicas e Farmac\u00eauticas, Universidade Federal de S\u00e3o Paulo, Diadema 09913-030, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1126\/science.aaa6097","article-title":"How to bolster the antifungal pipeline","volume":"347","author":"Denning","year":"2015","journal-title":"Science"},{"key":"ref_2","first-page":"271","article-title":"Invasive Fungal Infection","volume":"116","author":"Wagener","year":"2019","journal-title":"Dtsch. \u00c4rzteblatt Int."},{"key":"ref_3","first-page":"785","article-title":"Epidemiology of endemic systemic fungal infections in Latin America","volume":"49","author":"Colombo","year":"2011","journal-title":"Med. 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