Blood transcriptomics to characterize key biological pathways and identify biomarkers for predicting mortality in melioidosis. Issue 1 (1st January 2021)

• Record Type: Journal Article
• Authors: Yimthin, Thatcha; Cliff, Jacqueline Margaret; Phunpang, Rungnapa; Ekchariyawat, Peeraya; Kaewarpai, Taniya; Lee, Ji-Sook; Eckold, Clare; Andrada, Megan; Thiansukhon, Ekkachai; Tanwisaid, Kittisak; Chuananont, Somchai; Morakot, Chumpol; Sangsa, Narongchai; Silakun, Wirayut; Chayangsu, Sunee; Buasi, Noppol; Day, Nicholas; Lertmemongkolchai, Ganjana; Chantratita, Wasun; Eoin West, T.; Chantratita, Narisara
• Is Part Of: Emerging microbes & infections. Volume 10:Issue 1(2021)
• Page Start: 8
• Page End: 18
• Publication Date: 2021-01-01
• Subjects: RNA-sequencing -- transcriptomics -- melioidosis -- biomarkers -- Burkholderia pseudomallei -- outcome -- immune response; Medical microbiology -- Periodicals; Communicable diseases -- Periodicals; Infection -- Periodicals; 616.9041
• DOI: 10.1080/22221751.2020.1858176
• Languages: English
• ISSNs: 2222-1751

Abstract

ABSTRACT: Melioidosis is an often lethal tropical disease caused by the Gram-negative bacillus, Burkholderia pseudomallei . The study objective was to characterize transcriptomes in melioidosis patients and identify genes associated with outcome. Whole blood RNA-seq was performed in a discovery set of 29 melioidosis patients and 3 healthy controls. Transcriptomic profiles of patients who did not survive to 28 days were compared with patients who survived and healthy controls, showing 65 genes were significantly up-regulated and 218 were down-regulated in non-survivors compared to survivors. Up-regulated genes were involved in myeloid leukocyte activation, Toll-like receptor cascades and reactive oxygen species metabolic processes. Down-regulated genes were hematopoietic cell lineage, adaptive immune system and lymphocyte activation pathways. RT-qPCR was performed for 28 genes in a validation set of 60 melioidosis patients and 20 healthy controls, confirming differential expression. IL1R2, GAS7, S100A9, IRAK3, and NFKBIA were significantly higher in non-survivors compared with survivors ( P < 0.005) and healthy controls ( P < 0.0001). The AUROCC of these genes for mortality discrimination ranged from 0.80-0.88. In survivors, expression of IL1R2, S100A9 and IRAK3 genes decreased significantly over 28 days ( P < 0.05). These findings augment our understanding of this severe infection, showing expression levels of specific genes are potential biomarkers to predict melioidosis outcomes.