For centuries, phytochemicals have been used to prevent and cure multiple health
ailments. Phytochemicals have been reported to have antioxidant, antidiabetic, antitussive,
antiparasitic, anticancer, and antimicrobial properties. Generally, the therapeutic use of phytochemicals
is based on tradition or word of mouth with few evidence-based studies. Moreover,
molecular level interactions or molecular targets for the majority of phytochemicals are unknown.
In recent years, antibiotic resistance by microbes has become a major healthcare concern.
As such, the use of phytochemicals with antimicrobial properties has become pertinent.
Natural compounds from plants, vegetables, herbs, and spices with strong antimicrobial properties
present an excellent opportunity for preventing and combating antibiotic resistant microbial
infections. ATP synthase is the fundamental means of cellular energy. Inhibition of
ATP synthase may deprive cells of required energy leading to cell death, and a variety of dietary
phytochemicals are known to inhibit ATP synthase. Structural modifications of phytochemicals
have been shown to increase the inhibitory potency and extent of inhibition. Sitedirected
mutagenic analysis has elucidated the binding site(s) for some phytochemicals on
ATP synthase. Amino acid variations in and around the phytochemical binding sites can result
in selective binding and inhibition of microbial ATP synthase. In this review, the therapeutic
connection between dietary phytochemicals and ATP synthase is summarized based on the
inhibition of ATP synthase by dietary phytochemicals. Research suggests selective targeting
of ATP synthase is a valuable alternative molecular level approach to combat antibiotic resistant