1887

Abstract

Purpose. Candida biofilm infections are frequently linked to the use of biomaterials and are of clinical significance because they are commonly resistant to antifungals. Clioquinol is an antiseptic drug and is effective against multidrug-resistant Candida. We investigated the effect of clioquinol and two other 8-hydroxyquinoline derivatives on Candida biofilm.

Methodology. The ability to inhibit biofilm formation, inhibit preformed biofilm and remove established biofilms was evaluated using in vitro assays on microtitre plates. The action of clioquinol on biofilm in intrauterine devices (IUDs) was also investigated, describing the first protocol to quantify the inhibitory action of compounds on biofilms formed on IUDs.

Results. Clioquinol was found to be the most effective 8-hydroxyquinoline derivative among those tested. It prevented more than 90 % of biofilm formation, which can be attributed to blockade of hyphal development. Clioquinol also reduced the metabolic activity of sessile Candida but the susceptibility was lower compared to planktonic cells (0.031–0.5 µg ml required to inhibit 50 % planktonic cells and 4–16 µg ml to inhibit 50 % preformed biofilms). On the other hand, almost complete removal of biofilms was not achieved for the majority of the isolates. Candida spp. also showed the ability to form biofilm on copper IUD; clioquinol eradicated 80–100 % of these biofilms.

Conclusion. Our results indicate a potential application in terms of biomaterials for 8-hydroxyquinoline derivatives. Clioquinol could be used as a coating to prevent morphological switching and thus prevent biofilm formation. Furthermore, clioquinol may have future applications in the treatment of Candida infections linked to the use of IUDs.

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2018-09-26
2020-01-22
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References

  1. Paiva LC, Vidigal PG, Donatti L, Svidzinski TI, Consolaro ME. Assessment of in vitro biofilm formation by Candida species isolates from vulvovaginal candidiasis and ultrastructural characteristics. Micron 2012;43:497–502 [CrossRef][PubMed]
    [Google Scholar]
  2. Mayer FL, Wilson D, Hube B. Candida albicans pathogenicity mechanisms. Virulence 2013;4:119–128 [CrossRef][PubMed]
    [Google Scholar]
  3. Paiva LC, Donatti L, Patussi EV, Svizdinski TI, Lopes-Consolaro ME. Scanning electron and confocal scanning laser microscopy imaging of the ultrastructure and viability of vaginal Candida albicans and non- albicans species adhered to an intrauterine contraceptive device. Microsc Microanal 2010;16:537–549 [CrossRef][PubMed]
    [Google Scholar]
  4. Chassot F, Negri MF, Svidzinski AE, Donatti L, Peralta RM et al. Can intrauterine contraceptive devices be a Candida albicans reservoir?. Contraception 2008;77:355–359 [CrossRef][PubMed]
    [Google Scholar]
  5. Auler ME, Morreira D, Rodrigues FF, Abr Ao MS, Margarido PF et al. Biofilm formation on intrauterine devices in patients with recurrent vulvovaginal candidiasis. Med Mycol 2010;48:211–216 [CrossRef][PubMed]
    [Google Scholar]
  6. Segal D, Gohar J, Huleihel M, Mazor M. Fetal death associated with asymptomatic intrauterine Candida albicans infection and a retained intrauterine contraceptive device. Scand J Infect Dis 2001;33:77–78[PubMed]
    [Google Scholar]
  7. Barth T, Broscheit J, Bussen S, Dietl J. Maternal sepsis and intrauterine fetal death resulting from Candida tropicalis chorioamnionitis in a woman with a retained intrauterine contraceptive device. Acta Obstet Gynecol Scand 2002;81:981–982 [CrossRef][PubMed]
    [Google Scholar]
  8. Ramage G, Rajendran R, Sherry L, Williams C. Fungal biofilm resistance. Int J Microbiol 2012;2012:1–14 [CrossRef]
    [Google Scholar]
  9. Vipulanandan G, Herrera M, Wiederhold NP, Li X, Mintz J et al. Dynamics of mixed- Candida species biofilms in response to antifungals. J Dent Res 2018;97:91–98 [CrossRef][PubMed]
    [Google Scholar]
  10. Fanning S, Mitchell AP. Fungal biofilms. PLoS Pathog 2012;8:e1002585 [CrossRef][PubMed]
    [Google Scholar]
  11. Sardi JC, Pitangui NS, Rodríguez-Arellanes G, Taylor ML, Fusco-Almeida AM et al. Highlights in pathogenic fungal biofilms. Rev Iberoam Micol 2014;31:22–29 [CrossRef][PubMed]
    [Google Scholar]
  12. Mao X, Schimmer AD. The toxicology of clioquinol. Toxicol Lett 2008;182:1–6 [CrossRef][PubMed]
    [Google Scholar]
  13. Nakae K, Yamamoto S, Shigematsu I, Kono R. Relation between subacute myelo-optic neuropathy (S.M.O.N.) and clioquinol: nationwide survey. Lancet 1973;1:171–173 [CrossRef][PubMed]
    [Google Scholar]
  14. Wehbe M, Malhotra AK, Anantha M, Lo C, Dragowska WH et al. Development of a copper-clioquinol formulation suitable for intravenous use. Drug Deliv Transl Res 2018;8:239–251 [CrossRef][PubMed]
    [Google Scholar]
  15. Zhang YH, Raymick J, Sarkar S, Lahiri DK, Ray B et al. Efficacy and toxicity of clioquinol treatment and A-beta42 inoculation in the APP/PSI mouse model of Alzheimer's disease. Curr Alzheimer Res 2013;10:494–506 [CrossRef][PubMed]
    [Google Scholar]
  16. Huntington Study Group Reach2HD Investigators Safety, tolerability, and efficacy of PBT2 in Huntington's disease: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet Neurol 2015;14:39–47 [CrossRef][PubMed]
    [Google Scholar]
  17. Finkelstein DI, Hare DJ, Billings JL, Sedjahtera A, Nurjono M et al. Clioquinol improves cognitive, motor function, and microanatomy of the alpha-synuclein hA53T transgenic mice. ACS Chem Neurosci 2016;7:119–129 [CrossRef][PubMed]
    [Google Scholar]
  18. Franklin RB, Zou J, Zheng Y, Naslund MJ, Costello LC. Zinc ionophore (clioquinol) inhibition of human ZIP1-deficient prostate tumor growth in the mouse ectopic xenograft model: a zinc approach for the efficacious treatment of prostate cancer. Int J Cancer Clin Res 2016;3:037 [CrossRef][PubMed]
    [Google Scholar]
  19. Pippi B, Reginatto P, Machado G, Bergamo VZ, Lana DFD et al. Evaluation of 8-Hydroxyquinoline derivatives as hits for antifungal drug design. Med Mycol 2017;55:763–773 [CrossRef][PubMed]
    [Google Scholar]
  20. Alsterholm M, Karami N, Faergemann J. Antimicrobial activity of topical skin pharmaceuticals - an in vitro study. Acta Derm Venereol 2010;90:239–245 [CrossRef][PubMed]
    [Google Scholar]
  21. Clinical And Laboratory Standards Institute (CLSI) Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts, Approved Standard – Third Edition. CLSI Document M27-A3 Clinical Laboratory Standards Institute; Wayne, PA, USA: 2008
    [Google Scholar]
  22. Chiou CC, Mavrogiorgos N, Tillem E, Hector R, Walsh TJ. Synergy, pharmacodynamics, and time-sequenced ultrastructural changes of the interaction between nikkomycin Z and the echinocandin FK463 against Aspergillus fumigatus. Antimicrob Agents Chemother 2001;45:3310–3321 [CrossRef][PubMed]
    [Google Scholar]
  23. Bachmann SP, Vandewalle K, Ramage G, Patterson TF, Wickes BL et al. In vitro activity of caspofungin against Candida albicans biofilms. Antimicrob Agents Chemother 2002;46:3591–3596 [CrossRef][PubMed]
    [Google Scholar]
  24. Stepanović S, Vuković D, Hola V, di Bonaventura G, Djukić S et al. Quantification of biofilm in microtiter plates: overview of testing conditions and practical recommendations for assessment of biofilm production by staphylococci. APMIS 2007;115:891–899 [CrossRef][PubMed]
    [Google Scholar]
  25. Shuford JA, Piper KE, Steckelberg JM, Patel R. In vitro biofilm characterization and activity of antifungal agents alone and in combination against sessile and planktonic clinical Candida albicans isolates. Diagn Microbiol Infect Dis 2007;57:277–281 [CrossRef][PubMed]
    [Google Scholar]
  26. Mowat E, Butcher J, Lang S, Williams C, Ramage G. Development of a simple model for studying the effects of antifungal agents on multicellular communities of Aspergillus fumigatus. J Med Microbiol 2007;56:1205–1212 [CrossRef][PubMed]
    [Google Scholar]
  27. Ramage G, vande Walle K, Wickes BL, López-Ribot JL. Standardized method for in vitro antifungal susceptibility testing of Candida albicans biofilms. Antimicrob Agents Chemother 2001;45:2475–2479 [CrossRef][PubMed]
    [Google Scholar]
  28. Pitts B, Hamilton MA, Zelver N, Stewart PS. A microtiter-plate screening method for biofilm disinfection and removal. J Microbiol Methods 2003;54:269–276 [CrossRef][PubMed]
    [Google Scholar]
  29. Pippi B, Lopes W, Reginatto P, Silva Fernanda Émili Klein, Joaquim AR et al. New insights into the mechanism of antifungal action of 8-hydroxyquinolines. Saudi Pharm J 2018; [CrossRef]
    [Google Scholar]
  30. Lu Y, Su C, Liu H. Candida albicans hyphal initiation and elongation. Trends Microbiol 2014;22:707–714 [CrossRef][PubMed]
    [Google Scholar]
  31. Nobile CJ, Johnson AD. Candida albicans Biofilms and Human Disease. Annu Rev Microbiol 2015;69:71–92 [CrossRef][PubMed]
    [Google Scholar]
  32. Ramage G, Saville SP, Wickes BL, López-Ribot JL. Inhibition of Candida albicans biofilm formation by farnesol, a quorum-sensing molecule. Appl Environ Microbiol 2002;68:5459–5463 [CrossRef][PubMed]
    [Google Scholar]
  33. Baillie GS, Douglas LJ. Role of dimorphism in the development of Candida albicans biofilms. J Med Microbiol 1999;48:671–679 [CrossRef][PubMed]
    [Google Scholar]
  34. Ramage G, Wickes BL, López-Ribot JL. Inhibition on Candida albicans biofilm formation using divalent cation chelators (EDTA). Mycopathologia 2007;164:301–306 [CrossRef][PubMed]
    [Google Scholar]
  35. Silva S, Negri M, Henriques M, Oliveira R, Williams DW et al. Candida glabrata, Candida parapsilosis and Candida tropicalis: biology, epidemiology, pathogenicity and antifungal resistance. FEMS Microbiol Rev 2012;36:288–305 [CrossRef][PubMed]
    [Google Scholar]
  36. Mermel LA, Farr BM, Sherertz RJ, Raad II, O'Grady N et al. Guidelines for the management of intravascular catheter-related infections. Clin Infect Dis 2001;32:1249–1272 [CrossRef][PubMed]
    [Google Scholar]
  37. Hawser SP, Douglas LJ. Resistance of Candida albicans biofilms to antifungal agents in vitro. Antimicrob Agents Chemother 1995;39:2128–2131 [CrossRef][PubMed]
    [Google Scholar]
  38. Khan MS, Ahmad I. Antibiofilm activity of certain phytocompounds and their synergy with fluconazole against Candida albicans biofilms. J Antimicrob Chemother 2012;67:618–621 [CrossRef][PubMed]
    [Google Scholar]
  39. Donlan RM, Costerton JW. Biofilms: survival mechanisms of clinically relevant microorganisms. Clin Microbiol Rev 2002;15:167–193 [CrossRef][PubMed]
    [Google Scholar]
  40. Demirezen S, Dirlik OO, Beksaç MS. The association of Candida infection with intrauterine contraceptive device. Cent Eur J Public Health 2005;13:32–34[PubMed]
    [Google Scholar]
  41. Parewijck W, Claeys G, Thiery M, van Kets H. Candidiasis in women fitted with an intrauterine contraceptive device. Br J Obstet Gynaecol 1988;95:408–410 [CrossRef][PubMed]
    [Google Scholar]
  42. Pfaller MA. Antifungal drug resistance: mechanisms, epidemiology, and consequences for treatment. Am J Med 2012;125:S3–S13 [CrossRef][PubMed]
    [Google Scholar]
  43. Lockhart SR. Current epidemiology of Candida infection. Clin Microbiol Newsl 2014;36:131–136 [CrossRef]
    [Google Scholar]
  44. Kim J, Sudbery P. Candida albicans, a major human fungal pathogen. J Microbiol 2011;49:171–177 [CrossRef][PubMed]
    [Google Scholar]
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