Tuberculosis caused by Mycobacterium tuberculosis remains a global health challenge. New biomarkers that support rapid and accurate TB diagnosis are urgently needed. MicroRNAs (miRNAs) are small non-coding RNAs that have recently come into prominence as promising biomarkers. This thesis explores the application of miRNAs as biomarkers in tuberculosis and explores their expression in macrophages.
Using real-time quantitative reverse transcriptase polymerase chain reaction panels we investigated the expression of 175 miRNAs in a test set of 20 pulmonary TB patients and 20 healthy controls. 87 miRNAs were differentially regulated. Ten miRNAs were selected for validation in a larger cohort with newly diagnosed pulmonary TB sampled before the commencement of antibiotic therapy and then over the course of therapy. From the ten miRNAs selected, five were differentially regulated in newly diagnosed TB subjects.
The capacity of M. tuberculosis to modulate miRNA expression in human macrophages was examined. Seven miRNAs were examined in human macrophages with and without M. tuberculosis infection. The expression of miRNA in M. tuberculosis infected macrophages largely mirrored the findings from the plasma with a few exceptions.
Based on the findings from this work, miRNAs demonstrate great promise in their role as a potential biomarker for TB diagnostics.