Recent advances in understanding the antibacterial properties of flavonoids

Antibiotic resistance is a major global problem and there is a pressing need to develop new therapeutic agents. Flavonoids are a family of plant-derived compounds with potentially exploitable activities including direct antibacterial activity, synergism with antibiotics, and suppression of bacterial virulence. In this review, recent advances towards understanding these properties are described. Information is presented on the ten most potently antibacterial flavonoids, and the five most synergistic flavonoid-antibiotic combinations tested in the last six years (identified from PubMed and ScienceDirect). Top of these respective lists are panduratin A with MICs of 0.06 to 2.0 μg/mL against Staphylococcus aureus, and epicatechin gallate which reduces oxacillin MICs as much as 512-fold. Research seeking to improve such activity, and understand structure-activity relationships is discussed. Proposed mechanisms of action are discussed too. In addition to direct and synergistic activities, flavonoids inhibit a number of bacterial virulence factors including quorum sensing signal receptors, enzymes, and toxins. Evidence of these molecular effects at the cellular level include in vitro inhibition of biofilm formation, inhibition of bacterial attachment to host ligands, and neutralisation of toxicity toward cultured human cells. In vivo evidence of bacterial pathogenesis being disrupted includes demonstrated efficacy against Helicobacter pylori infection and S. aureus α-toxin intoxication.