Combinatorial genetics approach to prevent and disrupt biofilm-associated infection
New scientific technologies continue to advance and can be leveraged to define drug resistance mechanisms from the perspectives of both the microbe and the host.
In this project, the team will use parallel combinatorial genetics to systematically identify combinations of novel regulators of drug resistance. The Lu lab has developed CombiGEM CRISPR (CGC) to screen and identify novel gene combinations in human immune cells having activity against tuberculosis and shigellosis.
The key requirements for the application of this system to Enterococci are (1) the ability to perform CRISPR-mediated gene editing, (2) the availability of inducible promoters and efficient DNA delivery systems, and (3) a robust and reliable host-pathogen infection system to screen and then validate gene perturbations. With the recent report of efficient CRISPR editing in Enterococci, the Lu lab expertise in CGC, and the Kline lab genetic toolbox and biofilm model systems, this team is poised to apply CGC for the first time to a Gram-positive pathogen in the context of biofilm-associated host-pathogen interactions.