Cranberry proanthocyanidin-chitosan composite nanoparticles (PAC-CHT NPs) were formulated using 2:1, 5:1, 10:1, 15:1 20:1, 25:1, and 30:1 PAC to CHT weight ratio to form round shaped particles. The PAC-CHT NPs were characterized by size, polydispersity, surface charge, morphology, and PAC content. PAC-CHT NPs bioactivity was measured by agglutination of extra-intestinal pathogenic Escherichia coli (ExPEC) and inhibition of gut epithelial cell invasion by ExPEC. Results indicate that by increasing the PAC to CHT ratio 10:1 to 30:1 formed stable nanoparticles with diameters of 122.8 to 618.7nm, a polydispersity index of approximated 0.4 to 0.5, and a zeta potential of 34.5 to 54.4mV. PAC-CHT NPs ratio 30:1 agglutinated ExPEC and decreased the ability of ExPEC to invade epithelial cells in a dose-dependent manner. PAC-CHT NPs ratio 10:1 to 30:1 form stable, round-shaped, and bioactive nanoparticles for potential applications in the treatment of ExPEC bacterial infections.

A smart wound dressing based on carrageenan ( kappa C), locust bean gum (LBG), and cranberry extract (CB) for monitoring bacterial wound infections was developed and characterized using UV-vis spectroscopy, FT-IR, and SEM. The mechanical, swelling, cytotoxic and pH sensor properties were also investigated. UV-vis spectra demonstrated that the obtained kappa C:LBG:CB hydrogel film exhibited a visible change of colors as it was immersed in PBS solution pH 5.0, 7.3 and 9.0. The spectra of FT-IR suggested that chemical interactions had occurred between kappa C and CB extract. The obtained kappa C:LBG:CB hydrogel film exhibited adequate mechanical properties and a swelling behavior dependent on pH. Cytotoxicity tests indicated that kappa C:LBG:CB hydrogel film had dose-dependent cytotoxicity against NIH 3T3 fibroblast cells. The in vitro studies using Staphylococcus aureus and Pseudomonas aeruginosa demonstrated that the color changes of the kappa C:LBG:CB hydrogel film could be observed by naked eyes, confirming the potential use of the obtained hydrogel film as a visual system for monitoring bacterial wound infections.

Non-typhoidal Salmonella enterica serovars continue to be an important food safety issue worldwide. Cranberry (Vaccinium macrocarpon Ait) fruits possess antimicrobial properties due to their various acids and phenolic compounds; however, the underlying mechanism of actions is poorly understood. We evaluated the effects of cranberry extracts on the growth rate of Salmonella enterica serovars Typhimurium, Enteritidis and Heidelberg and on the transcriptomic profile of Salmonella Enteritidis to gain insight into phenotypic and transcriptional changes induced by cranberry extracts on this pathogen. An ethanolic extract from cranberry pomaces (KCOH) and two of its sub-fractions, anthocyanins (CRFa20) and non-anthocyanin polyphenols (CRFp85), were used. The minimum inhibitory (MICs) and bactericidal (MBCs) concentrations of these fractions against tested pathogens were obtained using the broth micro-dilution method according to the Clinical Laboratory Standard Institute's guidelines. Transcriptional profiles of S. Enteritidis grown in cation-adjusted Mueller-Hinton broth supplemented with or without 2 or 4 mg/ml of KCOH were compared by RNASeq to reveal gene modulations serving as markers for biological activity. The MIC and MBC values of KCOH were 8 and 16 mg/mL, respectively, against all tested S. enterica isolates. The MIC value was 4 mg/mL for both CRFa20 and CRFp85 sub-fractions, and a reduced MBC value was obtained for CRFp85 (4 mg/ml). Treatment of S. Enteritidis with KCOH revealed a concentration-dependent transcriptional signature. Compared to the control, 2 mg/ml of KCOH exposure resulted in 89 differentially expressed genes (DEGs), of which 53 and 36 were downregulated and upregulated, respectively. The upregulated genes included those involved in citrate metabolism, enterobactin synthesis and transport, and virulence. Exposure to 4 mg/ml KCOH led to the modulated expression of 376 genes, of which 233 were downregulated and 143 upregulated, which is 4.2 times more DEGs than from exposure to 2 mg/ml KCOH. The downregulated genes were related to flagellar motility, Salmonella Pathogenicity Island-1 (SPI-1), cell wall/membrane biogenesis, and transcription. Moreover, genes involved in energy production and conversion, carbohydrate transport and metabolism, and coenzyme transport and metabolism were upregulated during exposure to 4 mg/ml KCOH. Overall, 57 genes were differentially expressed (48 downregulated and 9 upregulated) in response to both concentrations. Both concentrations of KCOH downregulated expression of hilA, which is a major SPI-1 transcriptional regulator. This study provides information on the response of Salmonella exposed to cranberry extracts, which could be used in the control of this important foodborne pathogen.

Recurrent urinary tract infection (rUTI) continues to challenge pediatric care providers. The diagnosis of an rUTI can be difficult, especially in young febrile children. Antibiotic resistance rates continue to rise, which limits oral treatment options. Prophylactic antibiotics are used commonly to manage rUTI, but their use increases the risk of rUTI with antibiotic-resistant strains without significantly reducing renal scarring. Alternative therapies for rUTI include probiotics and anthocyanidins (eg, cranberry extract) to reduce gut colonization by uropathogens and prevent bacterial adhesion to uroepithelia, but efficacy data for these treatments are sparse. The future of rUTI care rests in addressing the following contemporary issues: best diagnostic practices, risk factors associated with rUTI, and the prevention of recurrent infection. In this review, we summarize the state of the art for each of these issues and highlight future studies that will aim to take an alternative approach to managing rUTI.

INTRODUCTION:Urinary tract infections (UTIs) represent a common and costly public health issue. The bacterium Escherichia coli is mainly responsible for most uncomplicated UTIs. Cranberry antibacterial effects have extensively been studied in order to understand the molecular mechanisms of action of its bioactive components and their clinical benefits against UTIs. In this respect, the present review aims to critically analyze the current clinical studies that have evaluated the efficacy of supplementing cranberry products against UTIs in different subpopulations.METHODS:PubMed database was comprehensively searched, using relative keywords in order to identify clinical trials exploring the efficacy of cranberry supplementation against UTIs.RESULTS:Current clinical evidence clearly indicates a possible benefit overall from the use of cranberries against UTIs. Cranberry consumption may prevent bacterial adherence to uroepithelial cells, reducing UTI related symptoms. Cranberry consumption could also decrease UTI related symptoms by suppressing inflammatory cascades as an immunologic response to bacterial invasion. The existing clinical trials have supported substantial evidence that the beneficial effects of cranberry against UTIs seem to be prophylactic by preventing infections recurrence; however, they exert low effectiveness in populations at increased risk for contracting UTIs. Moreover, a lack of cost-effectiveness for cranberry supplementation has been highlighted.CONCLUSIONS:Additional well-designed, double-blind, placebo-controlled clinical trials that use standardized cranberry products for long study periods are strongly recommended in order to determine the efficiency of cranberry on the prevention of UTIs in susceptible populations. At present, cranberry supplementation can safely be suggested as complementary therapy in women with recurrent UTIs.

We conducted a prospective study with the aim to evaluate the efficacy and safety of standardized cranberry capsules as prophylaxis in children with recurrent Urinary Tract Infections (UTIs). Therefore, children and adolescents, aged 2-18 years, with history of recurrent UTIs, were recruited for the study and randomized to receive cranberry in a standardized dose of cranberry extract 125 mg (proanthocyanidins 7.2%), vitamin C 7.5 mg and vitamin E 2.5 mg or not. They were followed for 1 year during which compliance, side-effects and UTI episodes were recorded. Children on cranberry compared to control group presented significantly lower percentage of UTIs, fewer days/year on antibiotic treatment and lower percentage of initiation of antimicrobial prophylaxis (p<0.05) due to UTIs recurrences. In addition, in the subgroup of children with vesicoureteral reflux we observe a significant difference between the cranberry and the controls group in the number of UTIs (p<0.05). No side effects in cranberry group were reported. Escherichia coli, Klebsiella and Proteus spp. in this order were the predominant species isolated in both groups in the beginning and also in the end of the study. A trend of decrease of E. coli episodes in the cranberry group before and after the treatment was documented (83.3% vs. 66.6%), however, this was not significant (p=0.28). It seems that the use of standardized dose of cranberry seems to be a secure and effective treatment for children with recurrent episodes of UTIs

LC-MS characterized cranberry extract from the fruits of Vaccinium macrocarpon inhibited under in vitro conditions the bacterial adhesion of Escherichia coli strain 2980 uropathogenic E. coli (UPEC strains UTI89, NU14) to T24 bladder cells and adhesion of UPEC strain CFT073 to A498 kidney cells in a concentration-dependent manner. Within a biomedical study, urine samples from 16 volunteers (8 male, 8 female) consuming cranberry extract for 7 d (900 mg/d) were analyzed for potential antiadhesive activity against UPEC by ex vivo experiments. Results indicated inhibition of adhesion of UPEC strain UTI89 to human T24 bladder cells. Subgroup analysis proved significant inhibition of bacterial adhesion in case of urine samples obtained from male volunteers while female urine did not influence the bacterial attachment. Differences between antiadhesive capacity of urine samples from male/female volunteers were significant. Protein analysis of the urinesamples indicated increased amounts of Tamm-Horsfall protein (THP, syn. uromodulin) in the active samples. Inhibition of bacterial adhesion by the urine samples was correlated to the respective amount of THP. As it is known that THP, a highly mannosylated glycoprotein, strongly interacts with FimH of UPEC, this will lead to a decreased interaction with uroplakin, a FimH-binding transmembrane protein of urothelial lining cells. From these data it can be concluded that the antiadhesive effect of cranberry after oral intake is not only related to the direct inhibition of bacterial adhesins by extract compounds but is additionally due to an induction of antiadhesive THP in the kidney.

Dark-colored fruit berries are a rich source of polyphenols that could provide innovative bioactive molecules as natural weapons against dental caries. High-quality extracts of cranberry, blueberry, and strawberry, and a combination of the three berry extracts (Orophenol), were used to treat 24-h-old Streptococcus mutans biofilms. The grown biofilms were treated with the berry extracts at concentrations ranging from 62.5 to 500 μg ml-1 . Treated biofilms were assessed for metabolic activity, acidogenicity, biovolumes, structural organization, and bacterial viability. The biofilms treated with the cranberry and Orophenol extracts exhibited the most significant reductions in metabolic activity, acid production, and bacterial/exopolysaccharide (EPS) biovolumes, while their structural architecture appeared less compact than the control-treated biofilms. The blueberry extract produced significant reductions in metabolic activity and acidogenicity only at the highest concentration tested, without significantly affecting bacterial/EPS biovolumes or biofilm architecture. Strawberry extracts had no significant effects on S. mutans biofilms. None of the berry extracts were bactericidal for S. mutans. The results indicate that cranberry extract was the most effective extract in disrupting S. mutans virulence properties without significantly affecting bacterial viability. This suggests a potential ecological role for cranberry phenols as non-bactericidal agents capable of modulating pathogenicity of cariogenic biofilms.

Quorum sensing (QS) and nucleotide-based second messengers are vital signaling systems that regulate bacterial physiology in response to changing environments. Disrupting bacterial signal transduction is a promising direction to combat infectious diseases, and QS and the second messengers are undoubtedly potential targets. In Vibrio cholerae, both QS and the second messenger 3', 5' - cyclic diguanylate (c-di-GMP) play a central role in controlling motility, motile-to-sessile life transition, and virulence. In this study, we found that water-soluble extract from the North American cranberry could significantly inhibit V. cholerae biofilm formation during the development/maturation stage by reducing the biofilm matrix production and secretion. The anti-biofilm effect by water-soluble cranberry extract was possibly through modulating the intracellular c-di-GMP level and was independent of QS and the QS master regulator HapR. Our results suggest an opportunity to explore more functional foods to fight stubborn infections through interference with the bacterial signaling systems.

Urinary tract infections (UTIs) are one the of the most common types of infections in adults older than 65 years of age. Preventing UTIs with prophylactic antibiotics increases the risk of side effects and microbial resistance, and is costly. Cranberry fruit and juices contain the compound proanthrocyanidins (PACs), specifically proanthrocyanidin-A, which exerts antiadhesion characteristics against bacteria. Cranberry products therefore have been an attractive, nonantibiotic preventative option for UTIs; however, the current literature supporting cranberry use in older adults is controversial. This could be multifactorial owing to the heterogeneity of the older population as well as inconsistencies in the recommended dose of PAC in the current literature. Evidence supports that cranberry may be beneficial in preventing UTIs in specific populations such as catheterassociated UTI and postradiotherapy prostate cancer. The cost of daily capsules versus the cost of preventing a UTI in older adults is an important consideration for initiating therapy.