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Title: Blood transcriptomics to characterize key biological pathways and identify biomarkers for predicting mortality in melioidosis
Authors: Thatcha Yimthin
Jacqueline Margaret Cliff
Rungnapa Phunpang
Peeraya Ekchariyawat
Taniya Kaewarpai
Ji Sook Lee
Clare Eckold
Megan Andrada
Ekkachai Thiansukhon
Kittisak Tanwisaid
Somchai Chuananont
Chumpol Morakot
Narongchai Sangsa
Wirayut Silakun
Sunee Chayangsu
Noppol Buasi
Nicholas Day
Ganjana Lertmemongkolchai
Wasun Chantratita
T. Eoin West
Narisara Chantratita
Udon Thani Center Hospital
London School of Hygiene & Tropical Medicine
Surin Hospital
Khon Kaen University
Faculty of Medicine, Ramathibodi Hospital, Mahidol University
Imperial College London
Mahidol University
Nuffield Department of Medicine
John A. Burns School of Medicine
Harborview Medical Center
Chiang Mai University
Sisaket Hospital
Roi Et Hospital
Nakhon Phanom Hospital
Mukdahan Hospital
Buriram Hospital
Keywords: Immunology and Microbiology;Medicine;Pharmacology, Toxicology and Pharmaceutics
Issue Date: 1-Jan-2021
Citation: Emerging Microbes and Infections. Vol.10, No.1 (2021), 8-18
Abstract: © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd. 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.
ISSN: 22221751
Appears in Collections:Scopus 2021

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