Written by Angeline A. De Leon, Staff Writer. Study suggests that cranberry alone is ineffective against all the uropathogenic Escherichia coli strains (UPEC); however, propolis potentiates the effect of cranberry on UPEC, representing a new strategy to prevent recurrent urinary tract infections.

Among the most common bacterial infections, urinary tract infections (UTI’s) are estimated to affect about 150 million individuals worldwide each year 1. One of the primary causes of UTI development is uropathogenic Escherichia coli (UPEC), a subgroup of pathogenic bacteria that infect extraintestinal sites 2. UPEC strains cause infection through adherence (of either structural factors, such as flagella, or secreted factors, such as toxins) to the epithelial (surface) cells in the urinary tract 3. Thus, strategies for combating UTI’s involve targeting bacterial adherence. Studies support the efficacy of both cranberry and propolis (resinous mixture produced by honey bees) in preventing UTI’s 4,5. Compounds in cranberries, A-type proanthocyanidins (PAC-A), can induce anti-microbial effects by reducing the surface of adherence 6, diminishing the mobility of UPEC 7, and/or modifying biofilm formation (the metabolic process by which microorganisms attach to and grow on a surface) 8. Possessing potent anti-inflammatory, anti-tumor, and immunomodulatory properties, propolis, when combined with cranberry, has been shown to influence UPEC anti-adhesion activity and even bacterial multiplication 9. While cranberry is known to influence the adhesion of UPEC 10, its effect on motility and biofilm formation is less clear. Therefore, in a 2018 study 11 published in PLoS ONE, researchers in France examined the effects of cranberry and propolis, alone and in combination, on the motility and biofilm formation of a collection of UPEC strains.

A panel of 12 UPEC strains were isolated from patients with cystitis, pyelonephritis, or asymptomatic UTI. A purified PAC juice extract was prepared from fresh cranberry fruit (standardized to a concentration of 190 µg/L PAC), and a hydroalcoholic extract of blended propolis (diluted in 50 mL phosphate buffered saline) was formulated. Two forms of motility were tested, swimming (movement of bacteria in a liquid medium) and swarming (movement of bacteria in a semi-liquid medium), using motility assays, which involved measurement of migration zones produced by UPEC strains in soft agar Luria-Bertani plates (in the presence of cranberry, propolis, cranberry plus propolis, or left untreated). Kinetics of early biofilm formation was analyzed using the Biofilm Ring Test, involving the incubation of standardized bacterial culture in the presence of magnetic beads and the measurement of their movement under magnet action (high mobility indicative of absence of biofilm formation). Late biofilm development was also assessed using the crystal violet method, involving the quantification of adherent bacterial cells using crystal violet dye.

Motility assays indicated that cranberry alone did not have a consistent effect on motility of UPEC strains (swarming reduced for all 12 strains, but swimming impacted in only 8 strains, p < 0.05 for all). However, exposure to cranberry in combination with propolis was associated with significantly reduced swarming in all 12 strains (p < 0.05 for all). Similarly, researchers observed that cranberry by itself had a variable effect on biofilm formation (reduced early biofilm formation in 5 strains, based on Biofilm Ring Test; reduced late biofilm formation in 6 strains, based on crystal violet assay; p < 0.0001 for all). Exposure to cranberry plus propolis impacted early biofilm formation in 5 UPEC strains (after 5 hours) (p < 0.0001 for all), while the combination of both was seen to significantly impact the complete (late) biofilm formation of all 12 strains (p < 0.0001 for all).

Results of the study suggest that while cranberry was helpful in inhibiting the pathogenesis of UTI’s, its favorable effects were unable to reach all UPEC strains. In contrast, the combination of propolis and cranberry produced a strong impact on both motility and biofilm formation, two key metabolic pathways involved in the development of UTI’s, in all 12 E. Coli strains. Cranberry and propolis were particularly effective in diminishing swarming and reducing late biofilm formation, thereby attenuating overall bacterial adherence. Researchers suggest that propolis may function to potentiate the protective effects of cranberry against UPEC and that their combined formulation may represent a promising treatment approach to UTI’s. Further research, however, is warranted to ascertain the exact biochemical mechanisms involved in propolis’ potentiation of cranberry’s therapeutic effects.

Source: Ranfaing J, Dunyach-Remy C, Lavigne J-P, et al. Propolis potentiates the effect of cranberry (Vaccinium macrocarpon) in reducing the motility and the biofilm formation of uropathogenic Escherichia coli. PLoS ONE. 2018; 13(8): e0202609. DOI: 10.1371/journal.pone.0202609.

© 2018 Ranfaing et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Posted October 21, 2019.

Angeline A. De Leon, MA, graduated from the University of Illinois at Urbana-Champaign in 2010, completing a bachelor’s degree in psychology, with a concentration in neuroscience. She received her master’s degree from The Ohio State University in 2013, where she studied clinical neuroscience within an integrative health program. Her specialized area of research involves the complementary use of neuroimaging and neuropsychology-based methodologies to examine how lifestyle factors, such as physical activity and meditation, can influence brain plasticity and enhance overall connectivity.

References:

  1. McLellan LK, Hunstad DA. Urinary tract infection: pathogenesis and outlook. Trends in molecular medicine. 2016;22(11):946-957.
  2. Flores-Mireles AL, Walker JN, Caparon M, Hultgren SJ. Urinary tract infections: epidemiology, mechanisms of infection and treatment options. Nature reviews microbiology. 2015;13(5):269.
  3. Terlizzi ME, Gribaudo G, Maffei ME. UroPathogenic Escherichia coli (UPEC) infections: virulence factors, bladder responses, antibiotic, and non-antibiotic antimicrobial strategies. Frontiers in microbiology. 2017;8:1566.
  4. Avorn J, Monane M, Gurwitz JH, Glynn RJ, Choodnovskiy I, Lipsitz LA. Reduction of bacteriuria and pyuria after ingestion of cranberry juice. Jama. 1994;271(10):751-754.
  5. Foo LY, Lu Y, Howell AB, Vorsa N. A-Type proanthocyanidin trimers from cranberry that inhibit adherence of uropathogenic P-Fimbriated escherichia c oli. Journal of natural products. 2000;63(9):1225-1228.
  6. Ahuja S, Kaack B, Roberts J. Loss of fimbrial adhesion with the addition of Vaccinum macrocarpon to the growth medium of P-fimbriated Escherchia coli. The Journal of urology. 1998;159(2):559-562.
  7. Hidalgo G, Chan M, Tufenkji N. Inhibition of Escherichia coli CFT073 fliC expression and motility by cranberry materials. Appl Environ Microbiol. 2011;77(19):6852-6857.
  8. Vollmerhausen T, Conneely A, Bennett C, Wagner V, Victor J, O’Byrne C. Visible and UVA light as a potential means of preventing Escherichia coli biofilm formation in urine and on materials used in urethral catheters. Journal of Photochemistry and Photobiology B: Biology. 2017;170:295-303.
  9. Foo LY, Lu Y, Howell AB, Vorsa N. The structure of cranberry proanthocyanidins which inhibit adherence of uropathogenic P-fimbriated Escherichia coli in vitro. Phytochemistry. 2000;54(2):173-181.
  10. Gupta A, Dwivedi M, Mahdi AA, Gowda GN, Khetrapal CL, Bhandari M. Inhibition of adherence of multi-drug resistant E. coli by proanthocyanidin. Urological research. 2012;40(2):143-150.
  11. Ranfaing J, Dunyach-Remy C, Lavigne J-P, Sotto A. Propolis potentiates the effect of cranberry (Vaccinium macrocarpon) in reducing the motility and the biofilm formation of uropathogenic Escherichia coli. PloS one. 2018;13(8):e0202609.