{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T06:07:08Z","timestamp":1789020428306,"version":"build-2803163510"},"reference-count":44,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteomics"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Paracoccidioidomycosis (PCM) is a major systemic mycosis in Latin America caused by\n                    <jats:italic>Paracoccidioides brasiliensis<\/jats:italic>\n                    , yet the contribution of aspartic proteases to fungal physiology and pathogenicity remains poorly understood. Here, we employed data\u2010independent acquisition (DIA)\u2010based quantitative proteomics to investigate the impact of pepstatin A\u2010mediated inhibition of aspartic proteases on the\n                    <jats:italic>P. brasiliensis<\/jats:italic>\n                    proteome. High\u2010coverage analysis identified up to 21,156 peptides and approximately 3000 proteins per condition, revealing progressive and time\u2010dependent proteomic remodeling after inhibitor exposure. Differential abundance analysis demonstrated changes in proteins associated with membrane organization, protein turnover, RNA metabolism, stress adaptation, and cellular homeostasis. Functional enrichment analyses indicated modulation of metabolic processes, oxidative phosphorylation\u2010associated proteins, and other biological functions related to fungal adaptation. Proteins associated with autophagy\u2010related processes were differentially regulated, while MDC staining revealed temporal changes in acidic vesicle formation, suggesting alterations in vesicle\u2010associated responses. Additionally, pepstatin A treatment reduced reactive oxygen species (ROS) production, consistent with changes in proteins related to oxidative metabolism. The inhibitor also impaired fungal adhesion to A549 pulmonary epithelial cells, indicating that aspartic proteases may influence host\u2013pathogen interactions through mechanisms beyond adhesin abundance alone. Collectively, these findings provide a systems\u2010level view of the cellular responses induced by aspartic protease inhibition and highlight the importance of these enzymes in regulating\n                    <jats:italic>P. brasiliensis<\/jats:italic>\n                    adaptation, homeostasis, and pathogenic potential.\n                  <\/jats:p>","DOI":"10.1002\/pmic.70180","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:35:06Z","timestamp":1789018506000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Aspartic Protease Inhibition Induces Proteomic Remodeling in\n                    <i>Paracoccidioides brasiliensis<\/i>"],"prefix":"10.1002","author":[{"given":"Sarah Fernandes","family":"Lima","sequence":"first","affiliation":[{"name":"Departamento de Ci\u00eancias Farmac\u00eauticas Instituto de Ci\u00eancias Ambientais, Qu\u00edmicas e Farmac\u00eauticas, Universidade Federal de S\u00e3o Paulo  S\u00e3o Paulo S\u00e3o Paulo 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 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo Brogliato","family":"de Moraes","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  S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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  S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro Henrique Corteletti","family":"Manfio","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  S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison Felipe Alencar","family":"Chaves","sequence":"additional","affiliation":[{"name":"Laboratory of Applied Toxinology, Center of Toxins, Immune\u2010response and Cell Signaling Butantan Institute  S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wagner Luiz","family":"Batista","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  S\u00e3o Paulo S\u00e3o Paulo Brazil"},{"name":"Departamento Microbiologia, Imunologia e Parasitologia Escola Paulista De Medicina, Universidade Federal de S\u00e3o Paulo  S\u00e3o Paulo 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