Proteomic analysis of serum samples of paracoccidioidomycosis patients with severe pulmonary sequel.

Autor: Santos ARD; Faculdade de Medicina, Universidade Federal de Mato Grosso do Sul (UFMS), Campo Grande, Brazil.; Faculdade de Medicina, Universidade Estadual Paulista (UNESP), Botucatu, Brazil., Dionizio A; Faculdade de Odontologia de Bauru (FOB), Universidade de São Paulo (USP), Bauru, Brazil., Fernandes MDS; Faculdade de Odontologia de Bauru (FOB), Universidade de São Paulo (USP), Bauru, Brazil., Buzalaf MAR; Faculdade de Odontologia de Bauru (FOB), Universidade de São Paulo (USP), Bauru, Brazil., Pereira B; Faculdade de Medicina, Universidade Estadual Paulista (UNESP), Botucatu, Brazil., Donanzam DFA; Faculdade de Medicina, Universidade Federal de Mato Grosso do Sul (UFMS), Campo Grande, Brazil.; Faculdade de Medicina, Universidade Estadual Paulista (UNESP), Botucatu, Brazil., Ribeiro SM; Faculdade de Medicina, Universidade Estadual Paulista (UNESP), Botucatu, Brazil., Paniago AMM; Faculdade de Medicina, Universidade Federal de Mato Grosso do Sul (UFMS), Campo Grande, Brazil., Cavalcante RS; Faculdade de Medicina, Universidade Estadual Paulista (UNESP), Botucatu, Brazil., Mendes RP; Faculdade de Medicina, Universidade Federal de Mato Grosso do Sul (UFMS), Campo Grande, Brazil.; Faculdade de Medicina, Universidade Estadual Paulista (UNESP), Botucatu, Brazil., Venturini J; Faculdade de Medicina, Universidade Federal de Mato Grosso do Sul (UFMS), Campo Grande, Brazil.; Faculdade de Medicina, Universidade Estadual Paulista (UNESP), Botucatu, Brazil.
Jazyk: angličtina
Zdroj: PLoS neglected tropical diseases [PLoS Negl Trop Dis] 2021 Aug 23; Vol. 15 (8), pp. e0009714. Date of Electronic Publication: 2021 Aug 23 (Print Publication: 2021).
DOI: 10.1371/journal.pntd.0009714
Abstrakt: Background: Pulmonary sequelae (PS) in patients with chronic paracoccidioidomycosis (PCM) typically include pulmonary fibrosis and emphysema. Knowledge of the molecular pathways involved in PS of PCM is required for treatment and biomarker identification.
Methodology/principal Findings: This non-concurrent cohort study included 29 patients with pulmonary PCM that were followed before and after treatment. From this group, 17 patients evolved to mild/ moderate PS and 12 evolved severe PS. Sera from patients were evaluated before treatment and at clinical cure, serological cure, and apparent cure. A nanoACQUITY UPLC-Xevo QT MS system and PLGS software were used to identify serum differentially expressed proteins, data are available via ProteomeXchange with identifier PXD026906. Serum differentially expressed proteins were then categorized using Cytoscape software and the Reactome pathway database. Seventy-two differentially expressed serum proteins were identified in patients with severe PS compared with patients with mild/moderate PS. Most proteins altered in severe PS were involved in wound healing, inflammatory response, and oxygen transport pathways. Before treatment and at clinical cure, signaling proteins participating in wound healing, complement cascade, cholesterol transport and retinoid metabolism pathways were downregulated in patients with severe PS, whereas signaling proteins in gluconeogenesis and gas exchange pathways were upregulated. At serological cure, the pattern of protein expression reversed. At apparent cure pathways related with tissue repair (fibrosis) became downregulated, and pathway related oxygen transport became upregulated. Additionally, we identified 15 proteins as candidate biomarkers for severe PS.
Conclusions/significance: Development of severe PS is related to increased expression of proteins involved in glycolytic pathway and oxygen exchange), indicative of the greater cellular activity and replication associated with early dysregulation of wound healing and aberrant tissue repair. Our findings provide new targets to study mechanisms of PS in PCM, as well as potential biomarkers.
Competing Interests: The authors have declared that no competing interest exists.
Databáze: MEDLINE
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