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

Author:

Santos Amanda Ribeiro dosORCID,Dionizio Aline,Fernandes Mileni da SilvaORCID,Buzalaf Marília Afonso RabeloORCID,Pereira BeatrizORCID,Donanzam Débora de Fátima AlmeidaORCID,Ribeiro Sergio MarroneORCID,Paniago Anamaria Mello MirandaORCID,Cavalcante Ricardo de Souza,Mendes Rinaldo PoncioORCID,Venturini JamesORCID

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 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.

Funder

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Fundação da Universidade Federal do Mato Grosso do Sul, UFMS/MEC, BRASIL

Publisher

Public Library of Science (PLoS)

Subject

Infectious Diseases,Public Health, Environmental and Occupational Health

Reference100 articles.

1. Phylogenetic analysis reveals a high level of speciation in the Paracoccidioides genus;MM Teixeira;Mol Phylogenet Evol,2009

2. Mortality due to systemic mycoses as a primary cause of death or in association with AIDS in Brazil: a review from 1996 to 2006;M Prado;Mem Inst Oswaldo Cruz,2009

3. Paracoccidioidomycosis: Current Perspectives from Brazil.;RP Mendes;Open Microbiol J.,2017

4. Brazilian guidelines for the clinical management of paracoccidioidomycosis.;MA Shikanai-Yasuda;Rev Soc Bras Med Trop.,2017

5. The lung in paracoccidioidomycosis: new insights into old problems;AN Costa;Clin Sao Paulo Braz,2013

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3