Version 1: Coincidence analysis of efflux pumps in the Escherichia coli pangenome

Global rates of multi-drug resistance continue to rise, posing a significant challenge in the fight against antimicrobial resistance worldwide. Multi-drug efflux pumps are a significant contributor to this burden. Understanding connections between the diverse network of efflux pump genes, and their interactions with other genes, is important for understanding the landscape of multi-drug resistance and devising new interventions to mitigate it. To address this issue, we have investigated how efflux pumps and accessory genes covary across genomes. Using genomic data from 200 publicly available Escherichia coli isolates, we constructed a pangenome and performed coincidence analyses using the bioinformatic tool Coinfinder. On an aggregate level, efflux pumps formed more coincident gene pairs within the accessory genome than avoidant gene pairs. Genes with a functional annotation associated with ‘transport’ had the highest representation for both coincident and avoidant gene pairs. In contrast, when specifically considering gene pairs where both genes were related to efflux pumps, avoidant pairs were more frequent, though some coincident pairs were also found—primarily between subcomponents that make up tripartite pumps, as well as between subcomponents and single unit efflux pumps). Further exploration and understanding on the role the efflux pumps from the accessory genome play and how it expresses itself, would result in developing novel strategies to target increasingly resistant bacteria.