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Gene Expression and Host Biomarkers for Predicting Mortality in Melioidosis

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Title:Gene Expression and Host Biomarkers for Predicting Mortality in Melioidosis
Authors:Andrada, Megan
Contributors:Nerurkar, Vivek (instructor)
Date Issued:13 Aug 2019
Abstract:Background: Melioidosis is a bacterial disease endemic in Northeast Thailand. This disease is difficult to diagnose and detect. There are currently no vaccines for this disease. There is a 35% mortality rate and 50% of infected patients develop sepsis. The immune responses of melioidosis patients are different from healthy donors, as demonstrated by differential gene expression in whole blood samples. These gene alterations may serve as host-based biomarkers for diagnosis and predicting outcomes.
Objectives: To validate the gene expression markers in blood of survivors vs. non-survivors with melioidosis that may be used for monitoring treatment response in melioidosis.
Materials and Methods: We identified a number of differentially expressed genes in the whole blood of non-survivors when compared with survivors diagnosed with melioidosis. Functional analysis was conducted to reveal major differentially expressed genes involved in biological processes of the immune system. Several immune signaling pathways of both innate immunity and adaptive immunity may play important roles and drive different outcomes in patients. To validate these markers, total RNA from whole blood of the patients and healthy individuals were extracted. Gene expression profiles of selected immune signaling genes were analyzed using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR). Nineteen non-survivor samples and 17 survivor samples were used in this study. The genes selected for this study were TLR2, TLR4, PFKFB3, RASGRP1, and CD160. Three housekeeping genes CycloA, TBP, and HPRT were also used for data analysis.
Results: TLR2 and TLR4 were highly expressed in melioidosis non-survivors compared to survivors. PFKFB3, RASGRP1, and CD160 did not show a significant difference in expression.
Conclusions: More genes and an increased sample size must be studied to further define treatment response for melioidosis patients. Some of the most significant genes or corresponding proteins will be further developed and evaluated as immunological markers for personalized treatment and possibly reducing the mortality of melioidosis.
Rights:Attribution-NonCommercial-NoDerivs 3.0 United States
Appears in Collections: MHIRT Poster Session 2019

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