Proanthocyanidin Interferes with Intrinsic Antibiotic Resistance Mechanisms of Gram‐Negative Bacteria

cells, or formation of biofilm, and emergence of antibiotic-resistant pathogens recalcitrant to treatment due to acquired resistance. Here, we report that a purified cranberry proanthocyanidin (cPAC) fraction potentiates the activity of a broad range of antibiotic classes against the opportunistic pathogens Escherichia coli, Proteus mirabilis, and Pseudomonas aeruginosa. cPAC was an effective potentiator against diverse bacterial lifestyles normally tolerant to antibiotics, such as biofilm bacteria, dormant cells, and in experimental models of chronic infections. Remarkably, when combined with tetracycline, cPAC was able to completely prevent the evolution of resistance in E. coli and P. aeruginosa. These results suggest that in combination with antibiotic therapy, cPAC has the potential to decrease the spread of antibiotic resistance and prolong the effectiveness of currently available drugs.