We profiled two single-gene deletion libraries of clinically relevant P. aeruginosa strains (PA01 and PA14) using over 200 chemical and environmental stressors. In these assays, we obtained quantitative measurements of mutant fitness, their ability to form biofilms, and their secondary metabolite profile.
The quantitative phenotypic and chemotypic signature for each mutant strain allows a) identifying novel gene functions; b) mapping of metabolic pathways; c) mapping of interconnections between functional cellular processes; d) addressing the role of horizontal gene transfer in network rewiring and gene repurposing; e) understanding how chemical perturbations affect the secondary metabolite profile; f) identifying novel secondary metabolites; etc.
My talk will present the foundations of our methodologies and include proof-of-principle examples highlighting the different types of information we obtained.
Additionally, I will discuss how we used untargeted genome wide screens to identify novel regulators of peptidoglycan synthesis in Escherichia coli.