miRNA as biomarkers for identifying resilience to mycobacterial infection

Pathogenic mycobacteria including Mycobacterium avium subsp. paratuberculosis (MAP), which is the causative agent of Johne’s Disease (JD), are able to manipulate host immune and transcriptomic pathways to cause chronic disease. Due to long and intermittent subclinical phases, where animals may be shedding environmentally stable bacteria, detection of MAP and diagnosis of disease using currently available methods is limited. There is a defined need for early detection of MAP infection and resilient animals during the silent subclinical phase to prevent further spread of bacteria and aid in the control of JD. Biomarkers are defined as objectively measurable indicators of normal or disease processes and may provide further insight into the interplay between host immune systems and pathogenic bacteria. microRNA (miRNA), a small non-coding subset of RNA, have been proposed as potential biomarker targets as they are highly stable and exert control over protein translation and gene expression. miRNA expression is dysregulated in mycobacterial infection, making them ideal candidates for biomarkers for the diagnosis, and differentiation between disease states, of paratuberculosis. To further characterise the contribution of differential miRNA expression in mycobacterial infection, functional analysis using a zebrafish-M. marinum will be utilised. Zebrafish present an ideal organism to investigate host-pathogen interactions in mycobacterial infections. The innate immune system is functional during early embryogenesis, while high fecundity allows for cost-effective, high throughput use in comparison to ruminant models of disease. The transparent nature of zebrafish is advantageous as it allows visualisation using fluorescent molecules and transgenic lines