In silico identification and in vitro evaluation of a protein-protein interaction inhibitor of Escherichia coli fatty acid biosynthesis

To combat the rise in antibiotic resistance, new targets must be identified and probes against them developed. Protein-protein interactions (PPI) of bacterial type II fatty acid biosynthesis (FAS-II) represent an untapped, yet rich area for new antibiotic discovery. Here, we present a computational and in vitro workflow for the discovery of new inhibitors of PPI in Escherichia coli FAS-II. As part of this study, we identified suramin, an existing treatment for African sleeping sickness, to effectively block the interaction of E. coli dehydratase FabA and the acyl carrier protein EcACP, with an IC50 = 85 mu M. This finding validates a workflow that combines in silico screening with in vitro PPI assays to identify probes appropriate for further optimization.