Researchers at the Institut National de la Recherche Scientifique in Montreal have found that compounds in cranberry juice may enhance the effectiveness of a commonly used antibiotic for urinary tract infections (UTIs) by altering how bacteria take up the drug. The findings, published in Applied and Environmental Microbiology, show that cranberry juice increased the activity of fosfomycin against uropathogenic Escherichia coli (UPEC) in laboratory testing and reduced the emergence antibiotic resistance mutations in 72% of the E. coli strains studied.
While the findings are encouraging, the researchers noted that the work didn’t show whether consumption of cranberry juice would have the same effects as those shown in the lab. “We don’t know if the metabolites will reach the infection,” said lead author Eric Déziel, PhD, a professor at Institut National de la Recherche Scientifique. “But if they could, then juice may increase the efficacy of antibiotic treatment.”
UTIs are most often caused by UPEC, which accounts for the majority of community-acquired infections and a substantial proportion of catheter-associated infections. Standard treatments include antibiotics such as trimethoprim-sulfamethoxazole, nitrofurantoin, and fosfomycin. While fosfomycin is a recommended first-line therapy because of its broad activity and low resistance rates, past studies have shown that some resistant variants can emerge through mutations that influence bacterial transport systems.
Cranberry products have long been associated with UTI prevention. Earlier theories surmised this was due to fruit’s acidity. Subsequent research, however, has identified specific compounds, including proanthocyanidins and fructose, that interfere with the ability of bacterial to attach to cells lining the urinary tract.
Déziel said that cranberry juice has a long history as folk remedy for preventing and treating urinary tract infections. It was the recent finding of the anti-adhesive properties that prompted further investigation into whether cranberry could influence antibiotic performance.
To test this, the research team exposed 32 clinical isolates of UPEC to cranberry juice in combination with fosfomycin under controlled laboratory conditions. The results showed that in 72% of the strains tested, cranberry juice increased the antibiotic’s inhibitory activity. At the same time, the frequency of spontaneous mutations conferring resistance dropped substantially, in some cases by several orders of magnitude.
The effects of the cranberry juice seems to involve changes in how bacterial cells regulate the uptake of sugars and, by extension, the antibiotic since fosfomycin enters bacterial cells through carbohydrate transport systems, primarily the GlpT and UhpT pathways. Resistance often arises when mutations reduce the activity of these transporters, which then limits the drug entering cells.
Specifically, cranberry juice reduced expression of the GlpT transporter while maintaining or promoting activity through the UhpT system. This shift allowed fosfomycin into the bacterial cell even as other pathways were downregulated. Reporter assays showed that this change sustained antibiotic uptake, while genomic sequencing revealed distinct mutation patterns depending on whether cranberry juice was present.
While the researchers were able to characterize the activity related to the presence of cranberry juice, the compounds responsible for this effect have not been fully identified. Déziel noted that “something in the cranberry juice” induces bacteria to increase uptake through one of these channels, leading to greater absorption of fosfomycin. Previous research has pointed to cranberry-derived molecules that interact with bacterial communication and adherence systems, but their role in modulating antibiotic transport has not been identified.
The study builds on earlier work from Déziel’s lab showing that cranberry extracts can act synergistically with antibiotics. The current research showed that this is also the case with cranberry juice itself. The hope is that simply consuming cranberry juice could produce the same effects as the extracts studied previously.
Despite the promising laboratory data, the researchers said that the findings cannot yet be translated to the clinic. It is still unclear whether the active compounds in cranberry juice are found at the needed concentrations in the urinary tract after consumption, or how much juice would be required to produce a measurable effect.
Future research will seek to identify the specific compounds responsible for the effects shown in this study, determine how they behave in vivo, and assess whether they can be incorporated into treatment strategies.
The post Natural Compounds in Cranberry Juice May Enhance Antibiotic Treatment of UTIs appeared first on Inside Precision Medicine.
platform from Element Biosciences profiled ~440,000 cells in a pooled CRISPR screen targeting 195 genes. Linking genetic perturbations to p65 subcellular localization and cell painting features in a single workflow enabled identification of known pathway components, uncovered regulatory roles for chromatin-modifying complexes, and improved interpretation of phenotypic outcomes using morphological features.