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

Abstract

Antibiotic resistance is spreading at an alarming rate among pathogenic bacteria in both medicine and agriculture. Interfering with the intrinsic resistance mechanisms displayed by pathogenic bacteria has the potential to make antibiotics more effective and decrease the spread of acquired antibiotic resistance. Here, it is demonstrated that cranberry proanthocyanidin (cPAC) prevents the evolution of resistance to tetracycline in Escherichia coli and Pseudomonas aeruginosa , rescues antibiotic efficacy against antibiotic‐exposed cells, and represses biofilm formation. It is shown that cPAC has a potentiating effect, both in vitro and in vivo, on a broad range of antibiotic classes against pathogenic E. coli , Proteus mirabilis , and P. aeruginosa . Evidence that cPAC acts by repressing two antibiotic resistance mechanisms, selective membrane permeability and multidrug efflux pumps, is presented. Failure of cPAC to potentiate antibiotics against efflux pump‐defective mutants demonstrates that efflux interference is essential for potentiation. The use of cPAC to potentiate antibiotics and mitigate the development of resistance could improve treatment outcomes and help combat the growing threat of antibiotic resistance.

Investigation of Antibacterial and Antiinflammatory Activities of Proanthocyanidins from Pelargonium sidoides DC Root Extract

“…Some authors have proposed the hypothesis that proanthocyanidins might increase bacterial membrane permeability and cause indirect metabolism decrease due to ATP and other intracellular metabolite loss [42,45]. A recent study shows that proanthocyanidins can potentiate antibiotics by acting via bacterial multidrug efflux pumps [46]. Thus, the disturbance in transmembrane transport indeed might be the cause of bacteriotoxicity.…”

Pentagalloyl glucose from Schinus terebinthifolia inhibits growth of carbapenem-resistant Acinetobacter baumannii

“…Resistance over the course of serial passaging was tested using a method adapted from Maisuria et al 54 . Briefly, a series of 21 microbroth dilution experiments for growth inhibition was carried with PGG or tetracycline against A. baumannii AB5075, using bacterial culture from the sub-MIC (0.5MIC) wells of each gradient to make the experimental culture for each subsequent experiment.…”

Commentary: Microbial Resistance Movements: An Overview of Global Public Health Threats Posed by Antimicrobial Resistance, and How Best to Counter

“…Also, alternatives to the existing antimicrobial drugs or supplementary agents are needed to reduce the burden of antimicrobial drug resistance. For instance, a recent publication from McGill University (in Montreal, Canada) has claimed that a cranberry extract can make the bacteria more sensitive to antibiotic treatment ( 20 ). Developing clinically viable quorum sensing inhibitors to supplement existing antimicrobial agents would be another research avenue to pursue ( 21 , 22 ).…”