Inhibition of Escherichia coli ATP synthase and cell growth by dietary pomegranate phenolics

Historically, people have been using pomegranate to alleviate many disease conditions. Pomegranate is known for its antiinflammatory, antioxidant, neuroprotective, anticancer, and antibacterial properties. In the current study, we examined effects of 8 dietary phenolics present in pomegranate (DPPs)-cyanidin-3-glucoside, cyanin chloride, delphinidin-3-glucoside, delphinidin-3,5-diglucoside, pelargonidin-3-glucoside, pelargonin chloride, punicalagin, and punicalin-on Escherichia coli ATP synthase and cell growth. DPPs caused complete or near complete (89%-100%) inhibition of wild-type E. coli ATP synthase and partial (5%-64%) inhibition of mutant enzymes alpha R283D, alpha E284R, beta V265Q, and gamma T273A. Growth inhibition of wild-type, null, and mutant strains in the presence of DPPs were lower than that of isolated wild-type and mutant ATP synthase. On a molar scale, cyanin chloride was the most potent, and pelargonidin-3-glucoside was the least effective inhibitor of wild-type ATP synthase. Partial inhibition of mutant enzymes confirmed that alpha R283D, alpha E284R, beta V265Q, and gamma T273A are essential in the formation of the phytochemical binding site. Our results establish that DPPs are potent inhibitors of wild-type E. coli ATP synthase and that the antimicrobial nature of DPPs can be associated with the binding and inhibition of microbial ATP synthase. Additionally, selective inhibition of microbial ATP synthase by DPPs is a useful method to combat antimicrobial resistance.

Automated summary

Pomegranate contains dietary phenolics that can inhibit Escherichia coli ATP synthase, potentially contributing to its antimicrobial properties. Selective inhibition of microbial ATP synthase by pomegranate compounds could be an important method to combat antimicrobial resistance.