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. 2023 Nov 2:8:347.
doi: 10.12688/wellcomeopenres.19809.2. eCollection 2023.

BurkHostGEN: a study protocol for evaluating variations in the Burkholderia pseudomallei and host genomes associated with melioidosis infection

Kesorn Angchagun  1 , Phumrapee Boonklang  1 , Chalita Chomkatekaew  1 , Sukritpong Pakdeerat  1 , Gumphol Wongsuwan  1 , Premjit Amornchai  1 , Vanaporn Wuthiekanun  1 , Salwaluk Panapipat  1 , Thatsanun Ngernseng  1 , Naomi Waithira  1 , Steve Walton  2 , Direk Limmathurotsakul  1 , Anoree Surawong  3 , Suwatthiya Siriboon  3 , Parinya Chamnan  3 , Narisara Chantratita  4 , Susie Dunachie  5 , Jukka Corander  2   6 , Emma E Davenport  2 , Julian Knight  7 , Julian Parkhill  8 , Sharon J Peacock  9 , Nicholas R Thomson  2 , Nicholas P J Day  1   5 , Claire Chewapreecha  1   2   10
Affiliations

BurkHostGEN: a study protocol for evaluating variations in the Burkholderia pseudomallei and host genomes associated with melioidosis infection

Kesorn Angchagun et al. Wellcome Open Res. .

Abstract

Background: Melioidosis is a frequently fatal disease caused by an environmental bacterium Burkholderia pseudomallei. The disease is prevalent in northeast Thailand, particularly among rice field farmers who are at risk of bacterial exposure through contact with contaminated soil and water. However, not all exposure results in disease, and infection can manifest diverse outcomes. We postulate that genetic factors, whether from the bacterium, the host or the combination of both, may influence disease outcomes. To address this hypothesis, we aim to collect, sequence, and analyse genetic data from melioidosis patients and controls, along with isolates of B. pseudomallei obtained from patients. Additionally, we will study the metagenomics of the household water supply for both patients and controls, including the presence of B. pseudomallei.

Methods: BurkHostGEN is an ongoing observational study being conducted at Sunpasitthiprasong Hospital, Ubon Ratchathani, Thailand. We are obtaining consent from 600 melioidosis patients and 700 controls, spanning both sexes, to collect 1 mL of blood for host DNA analysis, 3 mL of blood for RNA analysis, as well as 5 L of household water supply for metagenomic analysis. Additionally, we are isolating B. pseudomallei from the melioidosis patients to obtain bacterial DNA. This comprehensive approach will allow us to identify B. pseudomallei and their paired host genetic factors associated with disease acquisition and severity. Ethical approvals have been obtained for BurkHostGEN. Host and bacterial genetic data will be uploaded to European Genome-Phenome Archive (EGA) and European Nucleotide Archive (ENA), respectively.

Conclusions: BurkHostGEN holds the potential to discover bacterial and host genetic factors associated with melioidosis infection and severity of illness. It can also support various study designs, including biomarker validation, disease pathogenesis, and epidemiological analysis not only for melioidosis but also for other infectious diseases.

Keywords: bioresources; diagnostics; epidemiology; genomics; melioidosis; microbiology.

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Conflict of interest statement

No competing interests were disclosed.

Figures

Figure 1.
Figure 1.. Study design.
BurkHostGEN aims to collect, sequence and investigate the genetics of melioidosis patients, the bacterium that cause the disease in patients, as well as the bacteria recovered from patient’s household water supply.
Figure 2.
Figure 2.. Power calculation.
( a) Sample size required to detect host differential host gene expression. ( b) sample size required for eQTL analysis. ( c) sample size required for bacterial GWAS for host 28-day mortality. eQTL, expression quantitative trait loci; GWAS, genome-wide association study; MAF, minor allele frequencies.
See this image and copyright information in PMC

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