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

Abstract

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 11 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.

Lymphatic filarial serum proteome profiling for identification and characterization of diagnostic biomarkers

“…DAVID (Database for Annotation, Visualization, and Integrated Discovery) [ 24 ] version 6.8 and PANTHER (Protein Annotation through Evolutionary Relationship) database version 16.0 [ 25 ]. The functional annotation was done by uploading a list of Uniprot accession numbers of differentially expressed proteins and mapping with Homo sapiens data set [ 26 ]. The gene ontology terms, biological processes, cellular components, molecular function, protein class, and pathway analysis for each dataset were obtained from PANTHER.…”

Avanços e desafios no diagnóstico de paracoccidioidomicose causada pelo complexo de espécies da paracoccidioides: revisão integrativa

“…A paracoccidioidomicose (PCM) é uma micose sistêmica granulomatosa causada por fungos termodimórficos do gênero Paracoccidioides spp., descrita pela primeira vez por Adolpho Lutz em 1908, sendo considerada uma doença endêmica na América Latina (Santos, et al, 2021). A Paracoccidioides spp., foi considerado por muito tempo uma única espécie intitulada Paracoccidioides brasiliensis.…”

Combined Silymarin and Cotrimoxazole Therapy Attenuates Pulmonary Fibrosis in Experimental Paracoccidioidomycosis

“…In recent years, our group has focused on the study of pulmonary sequelae in patients with CF-PCM, and our findings have shown pro-fibrotic alterations since diagnosis along with prolonged systemic and low-grade pro-inflammatory profiles during and after a complete and successful antifungal therapy [ 6 , 7 , 8 , 9 , 10 ]. In addition, we previously established a murine model of pulmonary PCM, in which BALB/c mice presented with intense pulmonary fibrosis (PF), and we evaluated antifibrotic drugs and combined antifungal therapies [ 11 ].…”