Abstract
There is a pressing need to develop new antimicrobial drugs because of the increasing resistance of pathogenic bacteria to existing antibiotics. The preliminary development and validation of a novel methodology for the high-throughput screening of antimicrobial compounds and inhibitors of bacterial motility is described. This method uses a bacterial motility swarming agar assay, combined with the use of offset inoculation of the wells in a standard, clear, 96-well plate, to enable rapid screening of compounds for potential antibiotic and antimotility properties with a standard absorbance microplate reader. Thus, the methodology should be compatible with 96-well laboratory automation technology used in drug discovery and chemical biology studies. To validate the screening method, the Genesis Plus structurally diverse library of 960 biologically active compounds was screened against a motile strain of the gram-negative bacterial pathogen