{"title":"Identification of potential targets in bone destruction by Talaromyces marneffei: Insights from data-independent acquisition proteomics.","authors":"Junhong Zhou, Deshuang Xi, Yilin Teng, Yanbin Feng, Baicheng Wan, Shaohui Zong, Gaofeng Zeng","doi":"10.1093/mmy/myaf063","DOIUrl":null,"url":null,"abstract":"<p><p>To investigate the molecular mechanisms of Talaromyces marneffei (TM)-induced bone destruction through proteomic analysis using Data-Independent Acquisition (DIA) technology. Bone tissue samples were collected from eight patients (four TM-infected cases, four non-infectious controls). Samples underwent histopathological evaluation (Hematoxylin and Eosin Staining and Wright-Giemsa staining), DIA proteomics analysis, and protein validation through immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). Comparative analysis between Control (Con) and Infected (Inf) groups showed similar demographics but significantly elevated inflammatory markers in Inf. Histopathology revealed extensive bone destruction, marked inflammatory infiltration, fibrinoid necrosis, and altered hematopoietic cell populations in Inf specimens compared to Con. DIA proteomics identified 5930 quantifiable proteins, with 509 differentially expressed proteins (DEPs) between groups. Gene ontology and Kyoto encyclopedia of genes and genomes pathway analyses revealed significant enrichment of inflammation and immune response-related functions in Inf. COMMD1 was significantly downregulated while IL-17 was upregulated in Inf, as validated by immunohistochemistry and ELISA. DIA proteomics identified downregulated COMMD1 and upregulated IL-17 in TM-induced bone destruction, suggesting potential diagnostic biomarkers and therapeutic targets through inflammatory pathway modulation.</p>","PeriodicalId":18586,"journal":{"name":"Medical mycology","volume":" ","pages":""},"PeriodicalIF":2.3000,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Medical mycology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/mmy/myaf063","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
引用次数: 0
Abstract
To investigate the molecular mechanisms of Talaromyces marneffei (TM)-induced bone destruction through proteomic analysis using Data-Independent Acquisition (DIA) technology. Bone tissue samples were collected from eight patients (four TM-infected cases, four non-infectious controls). Samples underwent histopathological evaluation (Hematoxylin and Eosin Staining and Wright-Giemsa staining), DIA proteomics analysis, and protein validation through immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). Comparative analysis between Control (Con) and Infected (Inf) groups showed similar demographics but significantly elevated inflammatory markers in Inf. Histopathology revealed extensive bone destruction, marked inflammatory infiltration, fibrinoid necrosis, and altered hematopoietic cell populations in Inf specimens compared to Con. DIA proteomics identified 5930 quantifiable proteins, with 509 differentially expressed proteins (DEPs) between groups. Gene ontology and Kyoto encyclopedia of genes and genomes pathway analyses revealed significant enrichment of inflammation and immune response-related functions in Inf. COMMD1 was significantly downregulated while IL-17 was upregulated in Inf, as validated by immunohistochemistry and ELISA. DIA proteomics identified downregulated COMMD1 and upregulated IL-17 in TM-induced bone destruction, suggesting potential diagnostic biomarkers and therapeutic targets through inflammatory pathway modulation.
期刊介绍:
Medical Mycology is a peer-reviewed international journal that focuses on original and innovative basic and applied studies, as well as learned reviews on all aspects of medical, veterinary and environmental mycology as related to disease. The objective is to present the highest quality scientific reports from throughout the world on divergent topics. These topics include the phylogeny of fungal pathogens, epidemiology and public health mycology themes, new approaches in the diagnosis and treatment of mycoses including clinical trials and guidelines, pharmacology and antifungal susceptibilities, changes in taxonomy, description of new or unusual fungi associated with human or animal disease, immunology of fungal infections, vaccinology for prevention of fungal infections, pathogenesis and virulence, and the molecular biology of pathogenic fungi in vitro and in vivo, including genomics, transcriptomics, metabolomics, and proteomics. Case reports are no longer accepted. In addition, studies of natural products showing inhibitory activity against pathogenic fungi are not accepted without chemical characterization and identification of the compounds responsible for the inhibitory activity.