Pangenome guided pharmacophore modelling of enterohemorrhagic Escherichia coli sdiA

Enterohemorrhagic Escherichia coli (EHEC) continues to be a significant public health risk. With the onset of next generation sequencing, whole genome sequences are a potential resource for predictive modelling of the different regulatory mechanism of pathogens, particularly quorum sensing. We used a pangenome approach to determine EHEC genome clustering, determine the synonymous and nonsynonymous mutations across the EHEC sdiA and modelled the associated amino acid changes. Across the EHEC population, nonsynonymous variants are notably absent in ligand binding site for quorum sensing, indicating that population wide conservation of sdiA ligand site can be targeted for potential prophylactic purposes. Applying pathotype-wide pangenomics as a guide for determining evolution of pharmacophore sites is a potential approach in drug discovery.