Center For AIDS Research

Jeffrey Collins, MD, MPH

Funded by: NIH CFAR Administrative Supplement

Project Period: 8/1/19 - 7/31/20



Metabalonics and Lipidomics to Identify Tuberculosis Biomarkers

Project Summary
Development of point-of-care diagnostic tests able to distinguish active tuberculosis (TB) disease as well as those with latent TB infection (LTBI) at high risk for progression is limited by a lack of known peripheral blood biomarkers. This project seeks to utilize a combined plasma metabolomics and lipidomics approach to further develop molecular signatures associated with the spectrum of TB infection and disease with the potential for biomarker development to inform new TB diagnostics. We will use plasma samples from a non-human primate (NHP) model of TB infection, latency, chemotherapy-mediated bacterial clearance, and progression to active TB to validate molecular signatures previously found to be associated with these disease phenotypes in clinical studies. This proposal builds on prior analyses of human plasma, which have shown metabolomic and lipidomic signatures may be able to identify persons active TB and high-risk LTBI. These complementary data from a validated animal model with clear time points of TB infection, clearance and progression to active TB disease will provide experimental validation of molecular signatures from human studies with the greatest potential for biomarker development. Identification of blood-based biomarkers associated with the spectrum of TB infection and disease will have the potential to inform the next generation of TB diagnostics.

Relevance
This study aims to describe plasma metabolomic and lipidomic phenotypes associated with the spectrum of TB infection and disease in a non-human primate model of TB infection, chemotherapy-mediated bacterial clearance and progression to active TB disease. This will provide experimental validation of plasma molecular signatures described in clinical studies with potential for development as novel blood-based biomarkers to inform point-of-care TB diagnostics.