New Strategies to Detect and Prevent Tuberculosis
This new collaborative program aims to discover and implement novel strategies for the detection and prevention of tuberculosis in humans. The program builds on recent discoveries in the Groves laboratories at Princeton that have elucidated pathways used by virulent mycobacteria to access the iron they need for propagation within human cells. The host-pathogen interaction for tuberculosis is extraordinarily complex since the bacterium exploits some aspects of normal cell function while inhibiting or deactivating others. However, little is known about the iron acquisition and transport pathways adapted by mycobacteria in vivo.
Fluorescence detection techniques are being developed in the Groves laboratories that allow direct observation of iron theft from the host cell by the invading bacterium. The project aims to apply high-level mass spectrometric techniques developed in the Rabinowitz laboratory to monitor changes in metabolite profiles within human cells upon exposure to mycobacterial siderophores. Our effort has made several discoveries recently that together appear to require a significant modification of current thinking regarding iron acquisition by the pathogen. It is the basic premise of the project that detection of siderophore production by the M. tuberculosis can be exploited as an early indication of infection. Further, the siderophore uptake pathway offers a new and highly specific avenue for drug delivery and therapy.
PIs
