Overview of the Project: A Rational Pipeline for Development of Novel Anti-TB Drug Regimens

The global community is becoming increasingly aware that the treatment even for drug susceptible tuberculosis is prolonged (8-9 months), and frequently ends in failure and the generation of drug-resistant strains. Treatment regimens require a cocktail of 3-4 antibiotics because the bacterial population in vivo is heterogeneous and exhibits differential antibiotic susceptibility that alters with disease state. While scientists and researchers are slowly developing new TB drugs, there is a lack of a rational pipeline to test and optimize drug/drug combinations, which includes emergent host-directed therapeutics.
In this new project, supported by the Mueller Health Foundation, the Russell Lab at Cornell University proposes building on their platform of single cell profiling of active Mycobacterium tuberculosis (Mtb) infection in vivo to assess the relative susceptibility of Mtb subpopulations to the actions of current and emerging anti-tuberculosis drugs. The goal is to generate a “road map” that connects drug susceptible and drug tolerant bacterial populations and facilitates the rational design of combinatorial anti-tuberculosis drug regimens to provide more effective coverage of the total bacterial population. This could increase efficacy and shorten the course of treatment.

About the Russell Lab at Cornell University

David G. Russell has over 40 years of experience working with infectious agents and has always focused on the host/pathogen interface. His lab at Cornell University includes post-docs and graduate students all actively engaged in projects that range from basic questions of bacterial metabolism and macrophage physiology, to more translational research linked to development of new therapeutics for tuberculosis. His lab also actively collaborates with groups in Sub-Saharan Africa to study human tuberculosis, more specifically in the context of concomitant HIV-1 infection.