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

Abstract

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 αR283D, αE284R, βV265Q, and γT273A. 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 αR283D, αE284R, βV265Q, and γT273A 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.