In both cell culture and a preliminary animal model, bacteria proved more sensitive to cranberry-antibiotic combos than to antibiotics alone. The combos, which in every case incorporated proanthocyanidin (cPACs) derived from cranberries, appear to suppress two antibiotic resistance mechanisms: selective membrane permeability and multidrug efflux pumps. In other words, when cPACs are present, antibiotics check into bacteria, but they don’t check out.

These findings emerged from studies conducted at McGill University, where scientists followed up on the popular notion that cranberry juice can help fight urinary tract infections. The scientists, led by chemical engineering professor Nathalie Tufenkji, decided to investigate cranberry molecules—specifically, cPACs—and how they might affect pathogenic bacteria. Ultimately, cPACs and antibiotics were jointly administered to bacteria responsible for urinary tract infections, pneumonia, and gastro-enteritis.

The scientists determined that pathogenic bacteria become more sensitive to lower doses of antibiotics. What’s more, the bacteria don’t develop resistance to the antibiotics.

Detailed findings were presented May 28 in the journal Advanced Science, in an article titled, “Proanthocyanidin Interferes with Intrinsic Antibiotic Resistance Mechanisms of Gram‐Negative Bacteria.”

“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,” wrote the article’s authors. “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.”

Analyses showed that the cranberry extract increases bacterial sensitivity to antibiotics by acting in two ways. First, it makes the bacterial cell wall more permeable to the antibiotic, and second, it interferes with the mechanism used by the bacteria to pump out the antibiotic. Consequently, the antibiotic penetrates more easily, and the bacteria have a harder time getting rid of it, which explains why the drug is effective at lower doses.

“Normally when we treat bacteria with an antibiotic in the lab, the bacteria eventually acquire resistance over time,” said Tufenkji, the study’s corresponding author. “But when we simultaneously treated the bacteria with an antibiotic and the cranberry extract, no resistance developed. We were very surprised by this, and we see it as an important opportunity.”

“These are really exciting results,” added coauthor Éric Déziel, a professor of microbiology at INRS (Institut national de la recherche scientifique) in Montreal. “The activity is generated by molecules called proanthocyanidins. There are several different kinds of proanthocyanidins, and they may work together to deliver this outcome. We’ll need to do more research to determine which ones are most active in synergy with the antibiotic.”

After confirming the activity of the cranberry molecules on bacterial culture, the researchers tested to determine whether the pattern persisted in a preliminary animal model: infected insects. Since the synergistic effect of the extract and the antibiotic was also observed in the insects, further experiments will be conducted to clearly identify the active molecules.

If the results are confirmed in animals, certain classes of antibiotics subject to high levels of resistance could be made useful again by using cranberry extract to boost their potential.

The article’s authors noted that further work is needed to verify the efficacy and safety of the combination treatment in an in vivo mammalian model. “Encouragingly, our data show that cPAC is able to enhance the efficacy of a broad spectrum of antibiotics,” the authors concluded. “The ability to potentiate the action of antibiotics in a patient could improve treatment outcomes and hinder the emergence of antibiotic‐resistant infections.”

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