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Team:Paris Bettencourt/Project/Overview
From 2013.igem.org
To defeat tuberculosis, we need new biotechnology. Our work will add 4 new tools to the anti-TB medical armamentarium. Detect - A CRISPR-based biosensor delivered by phage and sequence-specific for antibiotic resistance. Target - An E. coli model hosting an essential mycobacterial metabolic pathway that could simplify drug screening. Infiltrate - A E. coli strain capable of entering infected macrophages and lysing mycobacteria. Sabotage - A non-lytic phage that spreads horizontally in a bacterial population and expresses an siRNA to knock down antibiotic resistance.
Detect
Diagnosing antibiotic resistance can improve treatment outcomes and slow the evolution of resistant strains. We propose a phage-delivered, CRISPR-based system that cuts specific DNA sequences and detects gene expression caused by DNA damage.
Target
M. tuberculosis grows slowly and is hard to study in the lab. We have transferred an essential mycobacterial metabolic pathway to E. coli, where is is easy to screen for targeted small-molecule inhibitors.
Infiltrate
An effective TB therapy must reach mycobacteria inside lung macrophages. In this system, E. coli express lysteriolysin O (LLO) to enter the macrophage cytosol and Trehalose Dimycolate Hydrolase (TDMH) to degrade the pathogen's membrane.
Sabotage
Totally drug-resistant TB (TDR-TB) is an established and growing problem. We have created a phage vector that delivers an siRNA capable of sabotaging drug resistance and restoring sensitivity. By reducing the fitness burden of our construct, we can promote its spread in a population.
What you need to know about TB
+33 1 44 41 25 22/25
team2013@igem-paris.org 
