Cranberries have been suggested to decrease the attachment of bacteria to uroepithelial cells (UC), thus preventing urinary tract infections, although the mechanisms are not well understood. A thermodynamic approach was used to calculate the Gibbs free energy of adhesion changes (DeltaG(adh)) for bacteria-UC interactions, based on measuring contact angles with three probe liquids. Interfacial tensions and DeltaG(adh) values were calculated for Escherichia coli HB101pDC1 (P-fimbriated) and HB101 (non-fimbriated) exposed to cranberry juice (0-27 wt.%). HB101pDC1 can form strong bonds with the Gal-Gal disaccharide receptor on uroepithelial cells, while HB101-UC interactions are only non-specific. For HB101 interacting with UC, DeltaG(adh) was always negative, suggesting favorable adhesion, and the values were insensitive to cranberry juice concentration. For the HB101pDC1-UC system, DeltaG(adh) became positive at 27wt.% cranberry juice, suggesting that adhesion was unfavorable. Acid-base (AB) interactions dominated the interfacial tensions, compared to Lifshitz-van der Waals (LW) interactions. Exposure to cranberry juice increased the AB component of the interfacial tension of HB101pDC1. LW interactions were small and insensitive to cranberry juice concentration. The number of bacteria attached to UC was quantified in batch adhesion assays and quantitatively correlated with DeltaG(adh). Since the thermodynamic approach should not agree with the experimental results when specific interactions are present, such as HB101pDC-UC ligand-receptor bonds, our results may suggest that cranberry juice disrupts bacterial ligand-UC receptor binding. These results help form the mechanistic explanation of how cranberry products can be used to prevent bacterial attachment to host tissue, and may lead to the development of better therapies based on natural products.

Scope: Atomic force microscopy (AFM) was used to directly measure the nanoscale adhesion forces between P-fimbriated Escherichia coli (E. coli) and human uroepithelial cells exposed to cranberry juice, in order to reveal the molecular mechanisms by which cranberry juice cocktail (CJC) affects bacterial adhesion.Methods and results: Bacterial cell probes were created by attaching P-fimbriated E. coli HB101pDC1 or non-fimbriated E. coli HB101 to AFM tips, and the cellular probes were used to directly measure the adhesion forces between E. coli and uroepithelial cells in solutions containing: 0, 2.5, 5, 10, and 27 wt% CJC. Macroscale attachment of E. coli to uroepithelial cells was measured and correlated to nanoscale adhesion force measurements. The adhesion forces between E. coli HB101pDC1 and uroepithelial cells were dose-dependent, and decreased from 9.32+/-2.37 nN in the absence of CJC to 0.75+/-0.19 nN in 27 wt% CJC. Adhesion forces between E. coli HB101 and uroepithelial cells were low in buffer (0.74+/-0.18 nN), and did not change significantly in CJC (0.78+/-0.18 nN in 27 wt% CJC; P=0.794).Conclusion: Our study shows that CJC significantly decreases nanoscale adhesion forces between P-fimbriated E. coli and uroepithelial cells.

Ulcer-associated dyspepsia is caused by infection with Helicobacter pylori. H. pylori is linked to a majority of peptic ulcers. Antibiotic treatment does not always inhibit or kill H. pylori with potential for antibiotic resistance. The objective of this study was to determine the potential for using phenolic phytochemical extracts to inhibit H. pylori in a laboratory medium. Our approach involved the development of a specific phenolic profile with optimization of different ratios of extract mixtures from oregano and cranberry. Subsequently, antimicrobial activity and antimicrobial-linked urease inhibition ability were evaluated. The results indicated that the antimicrobial activity was greater in extract mixtures than in individual extracts of each species. The results also indicate that the synergistic contribution of oregano and cranberry phenolics may be more important for inhibition than any species-specific phenolic concentration. Further, based on plate assay, the likely mode of action may be through urease inhibition and disruption of energy production by inhibition of proline dehydrogenase at the plasma membrane.

Cranberry juice has long been believed to benefit the prevention and treatment of urinary tract infections (UTIs). As the first step in the development of infection, bacterial adhesion is of great research interest, yet few studies have addressed molecular level adhesion in this context. P-fimbriated Escherichia coli play a major role in the development of a serious type of UTI, acute pyelonephritis. Experiments were conducted to investigate the molecular-scale effects of cranberry juice on two E. coli strains: HB101, which has no fimbriae, and the mutant HB101pDC1 which expresses P-fimbriae. Atomic force microscopy (AFM) was used to investigate both bacterial surface characteristics and adhesion forces between a probe surface (silicon nitride) and the bacteria, providing a direct evaluation of bacterial adhesion and interaction forces. Cranberry juice affected bacterial surface polymer and adhesion behavior after a short exposure period (3 h). Cranberry juice affected the P-fimbriated bacteria by decreasing the adhesion forces between the bacterium and tip and by altering the conformation of the surface macromolecules on E. coli HB101pDC1. The equilibrium length of polymer (P-fimbriae) on this bacterium decreased from approximately 148 to approximately 48 nm upon being exposed to cranberry juice. Highly acidic conditions were not necessary for the prevention of bacterial adhesion, since neutralization of cranberry juice solutions to pH = 7.0 allowed us to observe differences in adhesion between the E. coli strains. Our results demonstrate molecular-level changes in the surfaces of P-fimbriated E. coli upon exposure to neutralized cranberry juice.

AIMS: To investigate the effects of berries and berry phenolics on pathogenic intestinal bacteria and to identify single phenolic compounds being responsible for antimicrobial activity.

METHODS AND RESULTS: Antimicrobial activity of eight Nordic berries and their phenolic extracts and purified phenolic fractions were measured against eight selected human pathogens. Pathogenic bacterial strains, both Gram-positive and Gram-negative, were selectively inhibited by bioactive berry compounds. Cloudberry and raspberry were the best inhibitors, and Staphylococcus and Salmonella the most sensitive bacteria. Phenolic compounds, especially ellagitannins, were strong inhibitory compounds against Staphylococcus bacteria. Salmonella bacteria were only partly inhibited by the berry phenolics, and most of the inhibition seemed to originate from other compounds, such as organic acids. Listeria strains were not affected by berry compounds, with the exception of cranberry. Phenolic compounds affect the bacteria in different mechanisms.

CONCLUSIONS: Berries and their phenolics selectively inhibit the growth of human pathogenic bacteria.

SIGNIFICANCE AND IMPACT OF THE STUDY: Antimicrobial properties of berries could be utilized in functional foods. Furthermore these compounds would be of high interest for further evaluation of their properties as natural antimicrobial agents for food and pharmaceutical industry

The majority of infectious diseases are initiated by the adhesion of pathogenic organisms to the tissues of the host. In many cases this adhesion is mediated by lectins present on the surface of the infectious organism that bind to complementary carbohydrates on the surface of the host tissues. Soluble carbohydrates recognized by the bacterial lectins block the adhesion of the bacteria to animal cells in vitro. Moreover, such carbohydrates have been shown to protect against experimental infection by lectin-carrying bacteria of different mammals, such as mice, rabbits, calves, and monkeys. Agents other than carbohydrates also block adhesion, as demonstrated with cranberry juice as well as with low and high molecular weight preparations isolated from the juice. Both kinds of preparation inhibited the adhesion in vitro of Escherichia coli to different animal cells. In addition, the high molecular weight material acted similarly on the adhesion of Helicobacter pylori to human gasrointenstinal cells, and on the coaggregation of oral bacteria. Furthermore, in limited clinical studies regular drinking of cranberry juice had a significant preventive effect on bacteriuria, and the high molecular weight constituent of the juices was also effective in decreasing the salivary level of Streptococus mutans, the major cause of tooth decay. Because the inhibitors of adhesion examined are not bactericidal, the selection of resistant inhibitor strains is unlikely to occur. Together, these findings may lead to new therapeutic strategies that are in dire need because of the world-wide increase in antibiotic resistant bacteria.

The sensitivity of a large number of antibiotic-resistant and nonresistant Helicobacter pylori isolates to the antiadhesion effect of a high-molecular-mass, nondialysable constituent of cranberry juice was tested. Confluent monolayers of gastric cell line in microtiter plate wells were exposed to bacterial suspensions prepared from 83 H. pylori isolates from antibiotic-treated and untreated patients in the presence and absence of the cranberry constituent. Urease assay was used to calculate the percentage of adhesion inhibition. In two thirds of the isolates, adhesion to the gastric cells was inhibited by 0.2 mg/mL of the nondialysable material. There was no relationship between the antiadhesion effect of the cranberry material and metronidazole resistance in isolates from either treated or untreated patients (N=35). Only 13 isolates (16%) were resistant to both the nondialysable material and metronidazole, and 30 (36%) were resistant to the nondialysable material alone. There was no cross-resistance to the nondialysable material and metronidazole. These data suggest that a combination of antibiotics and a cranberry preparation may improve H. pylori eradication.

No abstract - The high-molecular-weight inhibitor of adhesin was partially purified from cranberry juice by gel-filtration chromatography. The product was heat-stable, resistant to trypsin, and nondialysable, and it inhibited the MR adhesin of al 20 urinary isolates tested in concentrations of 12 to 25 µg per milliliter. On the basis of these results, together with those of earlier studies, we suggest that the antiadhesive agents in juices from vaccinium berries may act in the gut (the source of most uropathogens), in the bladder, or both by preventing colonization of these sites.

Dental biofilm harbouring oral bacteria is highly correlated with the progression of dental diseases. Disruption of biofilm formation via anti-adhesion agents is an alternative means to the antibacterial approach. Previous studies have shown that high molecular weight non-dialysable material (NDM) derived from cranberry juice inhibits the adhesion of Escherichia coli and the coaggregation of a variety of oral bacteria. In addition, it inhibits the formation of glucans and fructans synthesised by GTF and FTF. In the present study, we examined the anti-adhesion effect of NDM on S. sobrinus. NDM promoted desorption of S. sobrinus from biofilm in the presence and absence of extracellular glucans and fructans, although the effect was more pronounced in the absence of these polysaccharides. Precoating of the bacteria with NDM reduced their ability to form biofilm. Our results indicate that NDM could be exploited as an anti-biofilm agent.

Cranberry juice contains high molecular weight materials (NDM) that inhibit bacterial adhesion to host cells as well as the co-aggregation of many oral bacteria. Because of its broad-spectrum activity, we investigated NDM's potential for inhibiting influenza virus adhesion to cells, and subsequent infectivity. Hemagglutination (HA) of red blood cells (RBC) caused by representatives of both influenza virus A subtypes (H1N1)and H3N2) and the B type was inhibited by NDM at concentrations of 125 microg/ml or lower, which is at least 20-fold lower than that usually found in cranberry juice. A dose-response effect of NDM on HA was demonstrated. The infectivity of the A and B types was significantly reduced by preincubation with NDM (250 microg/ml), as reflected by the lack of cytopathic effect on Madine-Darby canine kidney (MDCK) cells and the lack of HA activity in the media of infected cells. The effect of NDM was also tested after A or B type viruses were allowed to adsorb to and penetrate the cells. Various levels of reduction in virus tissue culture infective dose TCID50 were observed. The effect was most pronounced when NDM was added several times to the infected MDCK cells. Our cumulative findings indicate that the inhibitory effect of NDM on influenza virus adhesion and infectivity may have a therapeutic potential.