An increase in p62/NBR1 levels in melioidosis patients of Sri Lanka exhibit a characteristic of potential host biomarker
| Autor: | Robert G. Ulrich, Cyra M Ranji, Mohan Natesan, Aruna D. De Silva, Enoka Corea, Kamal U Saikh |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
Male 0301 basic medicine Microbiology (medical) autophagy Burkholderia pseudomallei Melioidosis 030231 tropical medicine Biology Microbiology Peripheral blood mononuclear cell Disease Diagnosis and Diagnostics Proinflammatory cytokine 03 medical and health sciences 0302 clinical medicine medicine Humans Pathogen Sri Lanka Intracellular parasite p62 Autophagy Intracellular Signaling Peptides and Proteins RNA-Binding Proteins NBR1 General Medicine biology.organism_classification medicine.disease cytokines 030104 developmental biology Immunology Leukocytes Mononuclear Biomarker (medicine) Female Biomarkers Research Article |
| Zdroj: | Journal of Medical Microbiology |
| ISSN: | 1473-5644 0022-2615 |
| DOI: | 10.1099/jmm.0.001242 |
| Popis: | Introduction. Melioidosis, caused by Burkholderia pseudomallei , in endemic areas, poses a challenge for treating the diseased populations without accurate diagnosis, and the disease-specific biomarkers linked with the infection have yet to be reported. Due to the invasive nature of the causative agent, Burkholderia pseudomallei , host innate effector mechanisms, including autophagy are known to be activated, resulting in differential expression of cellular proteins and immune markers. Identification of a disease-specific biomarker associated with B. pseudomallei infection will be helpful to facilitate rapid confirmation of melioidosis, which would enable early treatment and therapeutic success. Aim. We aimed to assess the levels of a host autophagy component, p62/NBR1, which function as a cargo-receptor in the process of autophagy activation leading to the degradation of ubiquitin-coated intracellular bacteria in which p62/NBR1 itself is degraded in the clearance of the pathogen. We further probed the extent of intracellular p62/NBR1 degradation and assessed its potential as a melioidosis biomarker. Methodology. We analysed peripheral blood mononuclear cell (PBMC) lysates using an ELISA-based assay for detecting cytosolic autophagy-related proteins p62/NBR1. We measured p62/NBR1 levels in diseased (confirmed B. pseudomallei infection) and non -diseased populations and utilized receiver operating characteristic (ROC) curve and max Youden index analysis for evaluating potential disease biomarker characteristics. Results. Our results revealed a three to fivefold increase in p62/NBR1 levels confirmed melioidosis cases compared to uninfected healthy donors. Comparable to p62/NBR1, levels of cytosolic LC3-I levels also increased, whereas the levels of degraded membrane bound form LC3-II was low, suggesting autophagy deficiency. Proinflammatory serum cytokine response, particularly IL-6, was consistently higher alongside B. pseudomallei infection in comparison to healthy controls. Conclusions. ROC curve and max Youden index analysis suggest that increased p62/NBR1 levels in diseased populations display characteristics of a potential disease biomarker in melioidosis and illustrates that an elevated p62/NBR1 level, in conjunction with B. pseudomallei infection associated with autophagy deficiency. |
| Databáze: | OpenAIRE |
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