Reconstructing the Mycobacterium Tuberculosis Metabolic Model
EMSL Project ID
40082
Abstract
Tuberculosis (TB) kills 3 million people every year, and the rising tide of drug-resistant TB threatens to overwhelm global health programs. New and improved drugs are urgently needed to shorten the duration of chemotherapy. To develop new drugs that kill bacteria in vivo we need to understand the microenvironments and metabolic pathways that play a role during M. tuberculosis (Mtb) infection of the host. The metabolism during host infection is impossible to predict since very little is known about the nature of the microenvironment of Mtb in vivo. This proposal will take a three-pronged approach to functionally annotating the Mtb genome including: (1) metabolomic analysis of both extracellular and intracellular metabolites with an emphasis on lipidomics from chemostat-adapted Mtb, (2) global analysis of metabolites and lipids from infected host tissue samples from non-human primates and human lung resection surgeries, and (3) chemical proteomic approaches using a 'toolbox' of condition-selective reactive molecules to identify protein targets critical for intracellular survival. Using these three complementary approaches will allow us to improve our understanding of the interactions and dynamics of the complex relationship of Mtb with the human host. The tools developed for these studies will be broadly applicable for simulating the dynamics of a myriad of host-pathogen interactions, not just TB-host.
Project Details
Project type
Large-Scale EMSL Research
Start Date
2010-10-01
End Date
2011-09-30
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members