Planta Med 2019; 85(02): 126-138
DOI: 10.1055/a-0755-7801
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Influence of Cranberry Extract on Tamm-Horsfall Protein in Human Urine and its Antiadhesive Activity Against Uropathogenic Escherichia coli

Birte Scharf
1   University of Münster, Institute of Pharmaceutical Biology and Phytochemistry, Münster, Germany
,
Jandirk Sendker
1   University of Münster, Institute of Pharmaceutical Biology and Phytochemistry, Münster, Germany
,
Ulrich Dobrindt
2   University Hospital Münster, Institute of Hygiene, Münster, Germany
,
Andreas Hensel
1   University of Münster, Institute of Pharmaceutical Biology and Phytochemistry, Münster, Germany
› Author Affiliations
Further Information

Publication History

received 17 August 2018
revised 26 September 2018

accepted 04 October 2018

Publication Date:
12 October 2018 (online)

Abstract

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 urine samples 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.

 
  • References

  • 1 Jepson RG, Williams G, Craig JC. Cranberries for preventing urinary tract infections. Cochrane Database Syst Rev 2012; (10) CD001321
  • 2 Rafsanjany N, Senker J, Brandt S, Dobrindt U, Hensel A. In vivo consumption of cranberry exerts ex vivo antiadhesive activity against FimH-dominated uropathogenic Escherichia coli: a combined in vivo, ex vivo, and in vitro study of an extract from Vaccinium macrocarpon . J Agric Food Chem 2015; 63: 8804-8818
  • 3 Foo LY, Lu Y, Howell AB, Vorsa N. A-Type proanthocyanidin trimers from cranberry that inhibit adherence of uropathogenic P-fimbriated Escherichia coli . J Nat Prod 2000; 63: 1225-1228
  • 4 Hidalgo G, Chan M, Tufenkji N. Inhibition of Escherichia coli CFT073 fliC expression and motility by cranberry materials. Appl Environ Microbiol 2011; 77: 6852-6857
  • 5 Di Martino P, Agniel R, Gaillard JL, Denys P. Effects of cranberry juice on uropathogenic Escherichia coli in vitro biofilm formation. J Chemother 2005; 17: 563-565
  • 6 Valentova K, Stejskal D, Bednar P, Vostalova J, Cíhalík C, Vecerova R, Koukalova D, Kolar M, Reichenbach R, Sknouril L, Ulrichova J, Simanek V. Biosafety, antioxidant status, and metabolites in urine after consumption of dried cranberry juice in healthy women: a pilot double-blind placebo-controlled trial. J Agric Food Chem 2007; 55: 3217-3224
  • 7 Tapiainen T, Jauhiainen H, Jaakola L, Salo J, Sevander J, Ikäheimo I, Pirttilä AM, Hohtola A, Uhari M. Biofilm formation and virulence of uropathogenic Escherichia coli in urine after consumption of cranberry-lingonberry juice. Eur J Clin Microbiol Infect Dis 2012; 31: 655-662
  • 8 Zafriri D, Ofek I, Adar R, Pocino M, Sharon N. Inhibitory activity of cranberry juice on adherence of type 1 and type P fimbriated Escherichia coli to eucaryotic cells. Antimicrob Agents Ch 1989; 33: 92-98
  • 9 Rzeppa S, Bittner K, Döll S, Dänicke S, Humpf H. Urinary excretion and metabolism of procyanidins in pigs. Mol Nutr Food Res 2012; 56: 653-665
  • 10 Zumdick S, Deters A, Hensel A. In vitro intestinal transport of oligomeric procyanidins (DP 2 to 4) across monolayers of Caco-2 cells. Fitoterapia 2012; 83: 1210-1217
  • 11 de Llano DG, Esteban-Fernández A, Sánchez-Patán F, Martínlvarez PJ, Moreno-Arribas MV, Bartolomé B. Anti-adhesive activity of cranberry phenolic compounds and their microbial-derived metabolites against uropathogenic Escherichia coli in bladder epithelial cell cultures. Int J Mol Sci 2015; 16: 12119-12130
  • 12 Kimble LL, Mathison BD, Kaspar KL, Khoo C, Chew BP. Development of a fluorometric microplate antiadhesion assay using uropathogenic Escherichia coli and human uroepithelial cells. J Nat Prod 2014; 77: 1102-1110
  • 13 Peron G, Sut S, Pellizzaro A, Brun P, Voinovich D, Castagliuolo I, DallʼAcqua S. The antiadhesive activity of cranberry phytocomplex studied by metabolomics: intestinal PAC-A metabolites but not intact PAC-A are identified as markers in active urines against uropathogenic Escherichia coli . Fitoterapia 2017; 122: 67-75
  • 14 Schwartz DJ, Kalas V, Pinkner JS, Chen SL, Spaulding CN, Dodson KW, Hultgren SJ. Positively selected FimH residues enhance virulence during urinary tract infection by altering FimH conformation. Proc Natl Acad Sci U S A 2013; 110: 15530-15537
  • 15 Serafini-Cessi F, Malagolini N, Cavallone D. Tamm-Horsfall glycoprotein: biology and clinical relevance. Am J Kidney Dis 2003; 42: 658-676
  • 16 Walsh JM, Ren X, Zampariello C, Polasky DA, McKay DL, Blumberg JB, Chen CO. Liquid chromatography with tandem mass spectrometry quantification of urinary proanthocyanin A2 dimer and its potential use as a biomarker of cranberry intake. J Sep Sci 2016; 39: 342-349
  • 17 Ohnishi R, Ito H, Kasajima N, Kaneda M, Kariyama R, Kumon H, Hatano T, Yoshida T. Urinary excretion of anthocyanins in humans after cranberry juice ingestion. Biosci Biotechnol Biochem 2006; 70: 1681-1687
  • 18 McKay DL, Chen CO, Zampariello CA, Blumberg JB. Flavonoids and phenolic acids from cranberry juice are bioavailable and bioactive in healthy older adults. Food Chem 2015; 168: 233-240
  • 19 Jensen HD, Struve C, Christensen SB, Krogfelt KA. Cranberry juice and combinations of its organic acids are effective against experimental urinary tract infection. Front Microbiol 2017; 8: 542
  • 20 Sarshar S, Brandt S, Asadi Karam MR, Habibi M, Bouzari S, Lechtenberg M, Dobrindt U, Qin X, Goycoolea FM, Hensel A. Aqueous extract from Orthosiphon stamineus leaves prevents bladder and kidney infection in mice. Phytomedicine 2017; 28: 1-9
  • 21 Sarshar S, Sendker J, Qin X, Goycoolea FM, Asadi Karam MR, Habibi M, Bouzari S, Dobrindt U, Hensel A. Antiadhesive hydroalcoholic extract from Apium graveolens fruits prevents bladder and kidney infection against uropathogenic E. coli . Fitoterapia 2018; 127: 237-244
  • 22 Pak J, Pu Y, Zhang ZT, Hasty DL, Wu XR. Tamm-Horsfall protein binds to type 1 fimbriated Escherichia coli and prevents E. coli from binding to uroplakin Ia and Ib receptors. J Biol Chem 2001; 276: 9924-9930
  • 23 Pruijm M, Ponte B, Ackermann D, Paccaud F, Guessous I, Ehret G, Pechère-Bertschi A, Vogt B, Mohaupt MG, Martin P, Youhanna SC, Nägele N, Vollenweider P, Waeber G, Burnier M, Devuyst O, Bochud M. Associations of urinary uromodulin with clinical characteristics and markers of tubular function in the general population. Clin J Am Soc Nephrol 2016; 11: 70-80
  • 24 European Pharmacopoeia 7.0/1220. General Methodology, Prüfung auf Gleichförmigkeit der Masse einzeldosierter Arzneiformen. Chapter 2.9.5. Eschborn, Germany: Govi-Verlag; 2011
  • 25 Bubeník J, Baresová M, Viklický V, Jakoubková J, Sainerová H, Donner J. Established cell line of urinary bladder carcinoma (T24) containing tumour-specific antigen. Int J Cancer 1973; 11: 765-773
  • 26 Miyazaki J, Ba-Thein W, Kumao T, Obata Yasuoka M, Akaza H, Hayshi H. Type 1, P and S fimbriae, and afimbrial adhesin I are not essential for uropathogenic Escherichia coli to adhere to and invade bladder epithelial cells. FEMS Immunol Med Microbiol 2002; 33: 23-26
  • 27 Giard DJ, Aaronson SA, Todaro GJ, Arnstein P, Kersey JH, Dosik H, Parks WP. In vitro cultivation of human tumors: establishment of cell lines derived from a series of solid tumors. J Natl Cancer Inst 1973; 51: 1417-1423
  • 28 Hultgren SJ, Schwan WR, Schaeffer AJ, Duncan JL. Regulation of production of type 1 pili among urinary tract isolates of Escherichia coli . Infect Immun 1986; 54: 613-620
  • 29 Chen SL, Hung C, Xu J, Reigstad CS, Magrini V, Sabo A, Blasiar D, Bieri T, Meyer RR, Ozersky P, Armstrong JR, Fulton RS, Latreille JP, Spieth J, Hooton TM, Mardis ER, Hultgren SJ, Gordon JI. Identification of genes subject to positive selection in uropathogenic strains of Escherichia coli: a comparative genomics approach. Proc Natl Acad Sci U S A 2006; 103: 5977-5982
  • 30 Welch RA, Burland V, Plunkett G, Redford P, Roesch P, Rasko D, Buckles EL, Liou S, Boutin A, Hackett J, Stroud D, Mayhew GF, Rose DJ, Zhou S, Schwartz DC, Perna NT, Mobley HLT, Donnenberg MS, Blattner FR. Extensive mosaic structure revealed by the complete genome sequence of uropathogenic Escherichia coli . Proc Natl Acad Sci U S A 2002; 99: 17020-17024
  • 31 Connell I, Agace W, Klemm P, Schembri M, Mărild S, Svanborg C. Type 1 fimbrial expression enhances Escherichia coli virulence for the urinary tract. Proc Natl Acad Sci U S A 1996; 93: 9827-9832
  • 32 Rafsanjany N, Lechtenberg M, Petereit F, Hensel A. Antiadhesion as a functional concept for protection against uropathogenic Escherichia coli: in vitro studies with traditionally used plants with antiadhesive activity against uropathognic Escherichia coli . J Ethnopharmacol 2013; 145: 591-597
  • 33 Langermann S, Palaszynski S, Barnhart M, Auguste G, Pinkner JS, Burlein J, Barren P, Koenig S, Leath S, Jones CH, Hultgren SJ. Prevention of mucosal Escherichia coli infection by FimH-adhesin-based systemic vaccination. Science 1997; 276: 607-611
  • 34 Elsinghorst EA. Measurement of invasion by gentamicin resistance. Meth Enzymol 1994; 236: 405-420
  • 35 Prior RL, Lazarus SA, Cao G, Muccitelli H, Hammerstone JF. Identification of procyanidins and anthocyanins in blueberries and cranberries (Vaccinium spp.) using high-performance liquid chromatography/mass spectrometry. J Agric Food Chem 2001; 49: 1270-1276
  • 36 Vvedenskaya IO, Rosen RT, Guido JE, Russell DJ, Mills KA, Vorsa N. Characterization of flavonols in cranberry (Vaccinium macrocarpon) powder. J Agric Food Chem 2004; 52: 188-195
  • 37 Turner A, Chen S, Nikolic D, van Breemen R, Farnsworth NR, Pauli GF. Coumaroyl iridoids and a depside from cranberry (Vaccinium macrocarpon). J Nat Prod 2007; 70: 253-258
  • 38 Lin L, Harnly JM. A screening method for the identification of glycosylated flavonoids and other phenolic compounds using a standard analytical approach for all plant materials. J Agric Food Chem 2007; 55: 1084-1096
  • 39 Iswaldi I, Gómez-Caravaca AM, Arráez-Román D, Uberos J, Lardón M, Segura-Carretero A, Fernández-Gutiérrez A. Characterization by high-performance liquid chromatography with diode-array detection coupled to time-of-flight mass spectrometry of the phenolic fraction in a cranberry syrup used to prevent urinary tract diseases, together with a study of its antibacterial activity. J Pharm Biomed Anal 2012; 58: 34-41
  • 40 Xiao Y, Hu Z, Yin Z, Zhou Y, Liu T, Zhou X, Chang D. Profiling and distribution of metabolites of procyanidin B2 in mice by UPLC-DAD-ESI-IT-TOF-MSn technique. Front Pharmacol 2017; 8: 231
  • 41 Stein-Chisholm R, Beaulieu J, Grimm C, Lloyd S. LC-MS/MS and UPLC-UV evaluation of anthocyanins and anthocyanidins during rabbiteye blueberry juice processing. Beverages 2017; 3: 56
  • 42 Vvedenskaya IO, Vorsa N. Flavonoid composition over fruit development and maturation in american cranberry, Vaccinium macrocarpon Ait. Plant Sci 2004; 167: 1043-1054