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

Vimal Maisuria (1) , Mira Okshevsky (1) , Eric Déziel (2) , Nathalie Tufenkji (1)

1 McGill University = Université McGill [Montréal, Canada]
2 INRS-IAF - Institut Armand Frappier

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.

Keywords: antimicrobial; anti‐biofilm; efflux pump; multidrug resistance; potentiation

Domains: Life Sciences [q-bio]; Microbiology and Parasitology; Pharmaceutical sciences; Immunology

Vimal Maisuria, Mira Okshevsky, Eric Déziel, Nathalie Tufenkji. Proanthocyanidin Interferes with Intrinsic Antibiotic Resistance Mechanisms of Gram‐Negative Bacteria. Advanced Science, 2019, 6 (15), pp.1802333. ⟨10.1002/advs.201802333⟩. ⟨pasteur-02275423⟩