PMID- 36983543 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230331 IS - 2309-608X (Electronic) IS - 2309-608X (Linking) VI - 9 IP - 3 DP - 2023 Mar 19 TI - Characterization of Aspartic Proteases from Paracoccidioides brasiliensis and Their Role in Fungal Thermo-Dimorphism. LID - 10.3390/jof9030375 [doi] LID - 375 AB - Paracoccidioidomycosis (PCM) is the most prevalent systemic mycosis in Latin America and is caused by fungi from the Paracoccidioides genus. 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-->yeast) in P. brasiliensis. In addition, these genes were modulated during thermo-dimorphism (M-->Y 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-pathogen relationship and P. brasiliensis biology. FAU - Silva, Rafael de Souza AU - Silva RS AUID- ORCID: 0000-0002-4002-0634 AD - Departamento Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, Sao Paulo 04023-062, SP, Brazil. FAU - Segura, Wilson Dias AU - Segura WD AUID- ORCID: 0000-0003-1134-5760 AD - Departamento Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, Sao Paulo 04023-062, SP, Brazil. FAU - Oliveira, Reinaldo Souza AU - Oliveira RS AUID- ORCID: 0000-0003-2420-1563 AD - Departamento de Ciencias Farmaceuticas, Instituto de Ciencias Ambientais, Quimicas e Farmaceuticas, Universidade Federal de Sao Paulo, Diadema 09913-030, SP, Brazil. FAU - Xander, Patricia AU - Xander P AD - Departamento de Ciencias Farmaceuticas, Instituto de Ciencias Ambientais, Quimicas e Farmaceuticas, Universidade Federal de Sao Paulo, Diadema 09913-030, SP, Brazil. FAU - Batista, Wagner Luiz AU - Batista WL AUID- ORCID: 0000-0003-0280-6828 AD - Departamento Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, Sao Paulo 04023-062, SP, Brazil. AD - Departamento de Ciencias Farmaceuticas, Instituto de Ciencias Ambientais, Quimicas e Farmaceuticas, Universidade Federal de Sao Paulo, Diadema 09913-030, SP, Brazil. LA - eng GR - 2020/14235-3/Sao Paulo Research Foundation/ GR - 311008/2020-8/National Council for Scientific and Technological Development/ GR - 2017/04592-0/Sao Paulo Research Foundation/ GR - 167849/2018-2/National Council for Scientific and Technological Development/ PT - Journal Article DEP - 20230319 PL - Switzerland TA - J Fungi (Basel) JT - Journal of fungi (Basel, Switzerland) JID - 101671827 PMC - PMC10053120 OTO - NOTNLM OT - Paracoccidioides OT - PbSap OT - aspartic protease OT - dimorphism OT - paracoccidioidomycosis OT - yapsin COIS- The authors declare no conflict of interest. EDAT- 2023/03/30 06:00 MHDA- 2023/03/30 06:01 PMCR- 2023/03/19 CRDT- 2023/03/29 01:44 PHST- 2022/12/20 00:00 [received] PHST- 2023/03/16 00:00 [revised] PHST- 2023/03/17 00:00 [accepted] PHST- 2023/03/30 06:01 [medline] PHST- 2023/03/29 01:44 [entrez] PHST- 2023/03/30 06:00 [pubmed] PHST- 2023/03/19 00:00 [pmc-release] AID - jof9030375 [pii] AID - jof-09-00375 [pii] AID - 10.3390/jof9030375 [doi] PST - epublish SO - J Fungi (Basel). 2023 Mar 19;9(3):375. doi: 10.3390/jof9030375.