4.3 Article

Clioquinol is a promising preventive morphological switching compound in the treatment of Candida infections linked to the use of intrauterine devices

Journal

JOURNAL OF MEDICAL MICROBIOLOGY
Volume 67, Issue 11, Pages 1655-1663

Publisher

MICROBIOLOGY SOC
DOI: 10.1099/jmm.0.000850

Keywords

clioquinol; 8-hydroxyquinoline derivatives; antifungal agents; Candida spp.; biofilm; intrauterine device

Categories

Funding

  1. Brazilian agency Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
  2. Brazilian agency Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
  3. Brazilian agency Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul (FAPERGS) [EDITAL 04/2016 - PRONUPEQ 2016]
  4. CNPq

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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 mu g ml(-1) required to inhibit 50% planktonic cells and 4-16 mu g ml(-1) 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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