Developing Transcriptional Markers for Detecting Infection with the Novel Tuberculosis Pathogen, Mycobacterium mungi, in Free-Ranging Banded Mongoose (Mungos mungo)

Abstract

Effectively developing robust predictive models for forecasting infectious disease dynamics over space and time relies on successful surveillance strategies to accurately assess host infection status. We are constantly refining these models to improve our understanding of transmission and persistence dynamics in host populations but are continuously challenged with difficulties in accurately diagnosing host infection status. These challenges are especially persistent for pathogens of the Mycobacterium tuberculosis Complex (MTBC), which cause tuberculosis (TB) disease in a wide array of mammalian hosts. These challenges are further exacerbated when working with MTBC pathogens in free-ranging wildlife hosts. Although TB disease in humans is a primary concern, TB in free-ranging wildlife hosts poses a large threat to human and animal health. One recently described and novel MTBC pathogen is Mycobacterium mungi, which infects the highly social, group-living banded mongoose (Mungos mungo). M. mungi poses a large threat to human and animal health as banded mongoose hosts thrive in urbanized areas and live in close proximity to humans, but despite this threat, accurately diagnosing M. mungi infection status remains a primary challenge. Here, I develop a host response-based assay for differentiating banded mongoose with clinical M. mungi disease from individuals that are putatively healthy using transcriptional biomarkers in whole blood. To our knowledge, this is the first evaluation of host response-based transcriptional signatures to detect TB infection in unstimulated whole blood collected from a free-ranging wildlife species.

I found that the expression of two genes, GBP5 and DUSP3, are significantly upregulated (GBP5, p < .05; DUSP3, p < .005) in banded mongoose with clinical M. mungi disease when compared to that of putatively healthy individuals. These results are consistent with studies of active M. tuberculosis disease in humans and support the use of host response-based assays using blood transcriptional biomarkers for diagnosing TB in free-ranging wildlife hosts. These findings are important for improving surveillance strategies for diagnosing M. mungi infection status in banded mongoose and will be essential in refining predictive models for forecasting transmission and persistence dynamics over space and time.