Urological Research

, Volume 40, Issue 2, pp 143–150 | Cite as

Inhibition of adherence of multi-drug resistant E. coli by proanthocyanidin

  • Ashish GuptaEmail author
  • Mayank Dwivedi
  • Abbas Ali Mahdi
  • G. A. Nagana Gowda
  • Chunni Lal Khetrapal
  • Mahendra Bhandari
Original Paper


Proanthocyanidin is commonly used for inhibiting urinary tract infection (UTI) of sensitive strains of Escherichia coli. The aim of this study was to investigate the effect of proanthocyanidin on adherence of uropathogenic multi-drug resistant E. coli to uroepithelial cells, which has not yet been investigated so far. Extracts of the purified proanthocyanidin were prepared from dried cranberry juice. Purity and structural assignment of proanthocyanidin was assessed using high performance liquid chromatography and 13C nuclear magnetic resonance spectroscopy, respectively. Subsequently, its affect on multi-drug resistant bacteria as well as quantification of anti-adherence bioactivity on human vaginal and bladder epithelial cells was appraised. Inhibition of adherence to an extent of about 70% with multi-drug resistant E. coli strains was observed on uroepithelial cell. The anti-adherence bioactivity of the proanthocyanidin was detected at concentrations of 10–50 µg/ml with significant bacteriuria. Probable proanthocyanidin through A-type linkages either combines to P-fimbriae of bacterial cells or modifies the structural entity of P-fimbriae and inhibits bacterial adherence to uroepithelial cells. The proanthocyanidin exhibited anti-adherence property with multi-drug resistant strains of uropathogenic P-fimbriated E. coli with in vitro study. Hence proanthocyanidin may be considered as an inhibitory agent for multi-drug resistant strains of E. coli adherence to uroepithelial cells.


Proanthocyanidin Bacterial adherence Multi-drug resistance E. coli 



Nuclear magnetic resonance


High performance liquid chromatography


Red blood cells

E. coli

Escherichia coli


Vaginal epithelial cells


Bladder epithelial cells




Colonization factor agar


Amoxicillin–Clavulanic Acid


Urinary tract infection


Phosphate buffer saline solution



We gratefully acknowledge the financial support from the Department of Science and Technology and council of scientific and industrial research, New Delhi, India.

Conflict of interest



  1. 1.
    Mysorekar IG, Hultgren JS (2006) Mechanisms of uropathogenic E. coli persistence and eradication from the urinary tract. Proc Natl Acad Sci USA 103:14170–14175PubMedCrossRefGoogle Scholar
  2. 2.
    Cohn EB, Schaeffer AJ (2004) Urinary tract infections in adults. Sci World J 4(Suppl 1):76–88CrossRefGoogle Scholar
  3. 3.
    Ronald A (2003) The etiology of urinary tract infection: traditional and emerging pathogens. Dis Mon 49(2):71–82PubMedCrossRefGoogle Scholar
  4. 4.
    Bahrani-Mougeot FK, Buckles EL, Lockatell CV, Hebel JR, Johnson DE, Tang CM, Donnenberg MS (2002) Type 1 fimbriae and extracellular polysaccharides are preeminent uropathogenic Escherichia coli virulence determinants in the murine urinary tract. Mol Microbiol 45:1079–1093PubMedCrossRefGoogle Scholar
  5. 5.
    Mulvey MA (2002) Adhesion and entry of uropathogenic Escherichia coli. Cell Microbiol 4(5):257–271PubMedCrossRefGoogle Scholar
  6. 6.
    Guay David RP (2009) Cranberry and urinary tract infections. Drugs 69:775–807PubMedCrossRefGoogle Scholar
  7. 7.
    Ofek I, Goldhar J, Zafriri D, Lis H, Adar R, Sharon N (1991) Anti-Escherichia coli adhesin activity of cranberry and blueberry juices. N Engl J Med 324:99–1599Google Scholar
  8. 8.
    Howell AB, Marderosian AD, Foo LY (1998) Inhibition of the adherence of P-fimbriated Escherichia coli to uroepithelial-cell surfaces by proanthocyanidine extracts from cranberries. N Engl J Med 339:1085–1086PubMedCrossRefGoogle Scholar
  9. 9.
    Howell AB, Foxman B (2002) Cranberry juice and adhesion of antibiotic-resistant uropathogens. JAMA 287:3082–3083PubMedCrossRefGoogle Scholar
  10. 10.
    Foo LY, Lu Y, Howell AB, Vorsa N (2000) The structure of cranberry proanthocyanidins which inhibit adherence of uropathogenic P-fimbriated E. coli in vitro. Phytochemistry 54:173–181PubMedCrossRefGoogle Scholar
  11. 11.
    Botto H, Neuzillet Y (2010) Effectiveness of a cranberry (Vaccinium macrocarpon) preparation in reducing asymptomatic bacteriuria in patients with an ileal enterocystoplasty. Scan J Urol Neprol 44:165–168CrossRefGoogle Scholar
  12. 12.
    Gunn JH (1878) Gunn’s newest family physician. PhiladelphiaGoogle Scholar
  13. 13.
    Clinical Laboratory Standard Institute (CLSI) (2007) Performance standards for antimicrobial susceptibility testing tests. M100-S17 CLSI, WayneGoogle Scholar
  14. 14.
    Stapleton AE, Fennell CL, Coder DM, Wobbe CL, Roberts PL, Stamm WE (2002) Precise and rapid assessment of E. coli adherence to vaginal epitelial cells by flow cytometry. Cytometry 50:31–37PubMedCrossRefGoogle Scholar
  15. 15.
    Cilento BG, Freeman MR, Schneck FX, Retik AB, Atala A (1994) Phenotypic and cytogenetic characterization of human bladder urothelia expanded in vitro. J Urol 152:665–670PubMedGoogle Scholar
  16. 16.
    Virkola R, Westerlund B, Holthofer H, Parkkinen J, Kekomaki M, Korhonen TK (1988) Binding characteristics of E. coli adhesins in human urinary bladder. Infect Immun 56:2615–2622PubMedGoogle Scholar
  17. 17.
    Gupta A, Dwivedi M, Nagana Gowda GA, Mahdi AA, Ayyagari A, Bhandari M, Khetrapal CL (2005) Rapid diagnosis of Pseudomonas aeruginosa induced urinary tract infection: use of proton NMR spectroscopy. NMR Biomed 18:293–299PubMedCrossRefGoogle Scholar
  18. 18.
    Gupta A, Dwivedi M, Nagana Gowda GA, Mahdi AA, Jain A, Ayyagari A, Roy R, Bhandari M, Khetrapal CL (2006) 1H NMR spectroscopy in the diagnosis of Klebsiella pneumoniae-induced urinary tract infection. NMR Biomed 19:1055–1061PubMedCrossRefGoogle Scholar
  19. 19.
    Gupta A, Dwivedi M, Mahdi AA, Nagana Gowda GA, Khetrapal CL, Bhandari M (2009) 1H nuclear magnetic resonance spectroscopy for identifying and quantifying common uropathogens: a metabolic approach to the urinary tract infection. BJU Int 104:236–244PubMedCrossRefGoogle Scholar
  20. 20.
    Gupta K, Chou MY, Howell A, Wobbe C, Grady R, Stapleton AE (2007) Cranberry products inhibits adherence of P-finbriated E. coli to primary cultured bladder and vaginal epithelial cells. J Urol 177:2357–2360PubMedCrossRefGoogle Scholar
  21. 21.
    Howell AB, Reed JD, Krueger CG, Winterbottom R, Cunningham DG, Leahy M (2005) A-type cranberry proanthocyanidins and uropathogenic bacterial anti-adhesion activity. Phytochemistry 66:2281–2291PubMedCrossRefGoogle Scholar
  22. 22.
    Howell AB, Botto H, Combescure C, Blanc-Potard AB, Gausa L, Matsumoto T, Tenke P, Sotto A, Lavigne JP (2010) Dosage effect on uropathogenic E. coli anti-adhesion activity in urine following consumption of cranberry powder standardized for proanthocyanidin content: a multicentric randomized double blind study. BMC Infect Dis 10(94):1–11Google Scholar
  23. 23.
    Zafriri D, Ofek I, Adar R, Pocino M, Sharon N (1989) Inhibitory activity of cranberry juice on adherence of type 1 and type P-fimbriated E. coli to eucaryotic cells. Antimicrob Agents Chemother 33:92–98PubMedGoogle Scholar
  24. 24.
    Cowan MM (1999) Plant products as antimicrobial agents. Clin Micro Rev 12:564–582PubMedGoogle Scholar
  25. 25.
    Kresty LA, Howell AB, Baird M (2008) Cranberry proanthocyanidins induce apoptosis and inhibit acid-induced proliferation of human esophageal adenocarcinoma cells. J Agric Food Chem 56:676–680PubMedCrossRefGoogle Scholar
  26. 26.
    La VD, Howell AB, Grenier D (2009) Cranberry proanthocyanidins inhibit MMP production and activity. J Dent Res 88:627–632PubMedCrossRefGoogle Scholar
  27. 27.
    Scalbert A (1991) Antimicrobial properties of tannins. Phytochemistry 30:3875–3883CrossRefGoogle Scholar
  28. 28.
    Howell AB (2007) Bioactive compounds in cranberries and their role in prevention of urinary tract infections. Mol Nutr Food Res 51:732–737PubMedCrossRefGoogle Scholar
  29. 29.
    Liu Y, Black MA, Caron L, Camesano TA (2006) Role of cranberry juice on molecular-scale surface characteristics and adhesion behavior of E. coli. Biotechnol Bioengineer 93:297–305CrossRefGoogle Scholar
  30. 30.
    Ahuja S, Kaack B, Roberts J (1998) Loss of fimbrial adhesion with the addition of Vaccinum Macrocarpon to the growth medium of P-fimbriated E. coli. J Urol 159:559–562PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Ashish Gupta
    • 1
    Email author
  • Mayank Dwivedi
    • 2
  • Abbas Ali Mahdi
    • 3
  • G. A. Nagana Gowda
    • 1
  • Chunni Lal Khetrapal
    • 1
  • Mahendra Bhandari
    • 4
  1. 1.Centre of Biomedical Magnetic ResonanceSanjay Gandhi Postgraduate Institute of Medical SciencesLucknowIndia
  2. 2.Department of MicrobiologyLady Hardinge Medical CollegeNew DelhiIndia
  3. 3.Department of BiochemistryChhatrapati Shahuji Maharaj Medical UniversityLucknowIndia
  4. 4.Vattikuti Urology InstituteHenry Ford Hospital SystemDetroitUSA

Personalised recommendations