A robust platform for chemical genomics in bacterial systems

• DOI: 10.1091/mbc.e15-08-0573
• Publication Date: 2016-01-21T04:35:09Z
• Authors: Shawn French; Chand Mangat; Amrita Bharat; Jean-Philippe Côté; Hirotada Mori; Eric D. Brown
• Keywords: Chemical genetics

While genetic perturbation has been the conventional route to probing bacterial systems, small molecules are showing great promise as probes for cellular complexity. Indeed, systematic investigations of chemical-genetic interactions can provide new insights into cell networks and often starting points understanding mechanism action novel chemical probes. We have developed a robust sensitive platform chemical-genomic in bacteria. The approach monitors colony volume kinetically using transmissive scanning measurements, enabling acquisition growth rates endpoint measurements. found that profiles were highly concentration, necessitating careful selection compound concentrations. Roughly 20,000,000 data collected 15 different antibiotics. 1052 identified biomass approach, adding rate resulted 1564 interactions, 50-200% increase depending on drug, with many genes uncharacterized or poorly annotated. interaction maps generated from these reveal common likely involved multidrug resistance. Additionally, deletion backgrounds exhibiting class-specific potentiation, revealing conceivable targets combination approaches drug discovery. This open is amenable kinetic screening any arrayable strain collection, be it prokaryotic eukaryotic.