{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T03:46:56Z","timestamp":1790567216770,"version":"4.1.0"},"reference-count":39,"publisher":"Microbiology Society","issue":"10","license":[{"start":{"date-parts":[[2020,10,1]],"date-time":"2020-10-01T00:00:00Z","timestamp":1601510400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000774","name":"Defense Threat Reduction Agency","doi-asserted-by":"crossref","award":["JSTO (CB3948) under USAMRIID project number 1324392"],"award-info":[{"award-number":["JSTO (CB3948) under USAMRIID project number 1324392"]}],"id":[{"id":"10.13039\/100000774","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100014055","name":"U.S. Army Medical Research Acquisition Activity","doi-asserted-by":"crossref","award":["(USAMRAA) contract number (W81XWH-14-C-0071"],"award-info":[{"award-number":["(USAMRAA) contract number (W81XWH-14-C-0071"]}],"id":[{"id":"10.13039\/100014055","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,10,1]]},"abstract":"\n Introduction.<\/jats:bold> Melioidosis, caused by \n \n Burkholderia pseudomallei<\/jats:ext-link>\n <\/jats:named-content>\n <\/jats:italic>, 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, \n \n Burkholderia pseudomallei<\/jats:ext-link>\n <\/jats:named-content>\n <\/jats:italic>, 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 \n \n B. pseudomallei<\/jats:ext-link>\n <\/jats:named-content>\n <\/jats:italic> infection will be helpful to facilitate rapid confirmation of melioidosis, which would enable early treatment and therapeutic success.<\/jats:p>\n \n Aim.<\/jats:bold> 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.<\/jats:p>\n \n Methodology.<\/jats:bold> 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 \n \n B. pseudomallei<\/jats:ext-link>\n <\/jats:named-content>\n <\/jats:italic> infection) and non -diseased populations and utilized receiver operating characteristic (ROC) curve and max Youden index analysis for evaluating potential disease biomarker characteristics.<\/jats:p>\n \n Results.<\/jats:bold> 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 \n \n B. pseudomallei<\/jats:ext-link>\n <\/jats:named-content>\n <\/jats:italic> infection in comparison to healthy controls.<\/jats:p>\n \n Conclusions.<\/jats:bold> 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 \n \n B. pseudomallei<\/jats:ext-link>\n <\/jats:named-content>\n <\/jats:italic> infection associated with autophagy deficiency.<\/jats:p>","DOI":"10.1099\/jmm.0.001242","type":"journal-article","created":{"date-parts":[[2020,8,20]],"date-time":"2020-08-20T16:15:52Z","timestamp":1597940152000},"page":"1240-1248","source":"Crossref","is-referenced-by-count":4,"title":["An increase in p62\/NBR1 levels in melioidosis patients of Sri Lanka exhibit a characteristic of potential host 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