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.

中文翻译：

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斯里兰卡的类oid病患者中p62 / NBR1水平的升高表现出潜在宿主生物标志物的特征。

介绍。由地方性假伯克霍尔德氏菌引起的类鼻osis病在没有准确诊断的情况下对治疗患病人群提出了挑战，与感染相关的疾病特异性生物标志物尚未报道。由于病原体的侵袭性，已知假性伯克霍尔德菌的宿主固有效应器机制（包括自噬）被激活，导致细胞蛋白和免疫标记物的差异表达。鉴定与假苹果芽孢杆菌感染相关的疾病特异性生物标记物将有助于促进快速诊断类腮腺炎，这将使早期治疗和治疗成功。目标。 我们旨在评估宿主自噬成分p62 / NBR1的水平，该成分在自噬激活过程中充当货物受体，导致泛素包被的细胞内细菌降解，其中p62 / NBR1自身的清除率降低病原体。我们进一步探查了细胞内p62 / NBR1降解的程度，并评估了其作为类弓形虫生物标志物的潜力。方法。我们使用基于ELISA的分析方法分析外周血单核细胞（PBMC）裂解物，以检测胞浆自噬相关蛋白p62 / NBR1。我们测量了患病（已确诊的假疟原虫）的p62 / NBR1水平。 感染和非疾病人群，并利用受试者工作特征（ROC）曲线和最大尤登指数分析来评估潜在的疾病生物标志物特征。结果。我们的结果表明，与未感染的健康捐献者相比，确诊为类胚瘤的p62 / NBR1水平增加了三到五倍。与p62 / NBR1相比，胞浆中LC3-I的水平也增加了，而从LC3-II降解的膜结合的水平却很低，表明自噬不足。与健康对照相比，与假苹果芽孢杆菌感染相比，促炎性血清细胞因子反应，尤其是IL-6始终较高。结论 ROC曲线和最大尤登指数分析表明，患病人群中升高的p62 / NBR1水平显示了类拟鼻虫病潜在疾病生物标志物的特征，并表明升高的p62 / NBR1水平与假性芽孢杆菌感染与自噬缺乏相关。