nÃo hà / O Complexo Candida parapsilosis compreende trÃs espÃcies, C. parapsilosis stricto sensu, C. metapsilosis e C. orthopsilosis, que possuem caracterÃsticas fenotÃpicas iguais, podendo ser diferenciadas apenas pelo genÃtipo utilizando a tÃcnica de PCR com enzima de restriÃÃo. O Complexo C. parapsilosis vem ganhando destaque na epidemiologia mundial da candidÃase por ser a 2a ou 3a espÃcies mais isolada, alÃm disso, relatos de resistÃncia a alguns antifÃngicos sÃo preocupantes. A calcineurina molÃcula responsÃvel, tambÃm, pela resistÃncia aos antifÃngicos e pensando em novos alvos moleculares para as drogas que o objetivo desse trabalho foi, avaliar o potencial sinÃrgico de antifÃngicos e do inibidor de calcineurina, ciclosporina A, contra formas planctÃnicas e biofilmes de cepas do Complexo C. parapsilosis de origens clÃnicas. Os ensaios de sensibilidade com anfotericina B, fluconazol, voriconazol, caspofungina e ciclosporina A foram realizadas pela tÃcnica de microdiluiÃÃo, em conformidade com as orientaÃÃes do Clinical Laboratory Standards Institute. Os testes de sinergismo contra cÃlulas planctÃnicas de cepas do Complexo C. parapsilosis foram realizados pelo mÃtodo de Checkerboard, em ensaio de microdiluiÃÃo. CombinaÃÃes formadas por antifÃngicos com ciclosporina A foram avaliados contra biofilmes em formaÃÃo e maduros, em placas de poliestireno, onde diferenÃas no padrÃo de sensibilidade aos antifÃngicos entre as espÃcies nÃo foram observadas, porÃm cepas de C. parapsilosis stricto sensu foram mais sensÃveis à ciclosporina A que C. orthopsilosis e C. metapsilosis. O sinergismo entre os antifÃngicos e ciclosporina A foi observado em cepas do Complexo C. parapsilosis. As combinaÃÃes formadas por antifÃngicos e ciclosporina A foram capazes de impedir o crescimento das espÃcies do Complexo na fase planctÃnica, bem como, na formaÃÃo de biofilme nas CIM10X e CIM50X e mostrou efeito inibitÃrio contra biofilmes maduros de C. parapsilosis stricto sensu, C. metapsilosis e C. orthopsilosis nas CIM50X. Os resultados obtidos reforÃam o potencial de inibiÃÃo da calcineurina fÃngica como uma abordagem promissora para aumentar a eficiÃncia de drogas antifÃngicas. / Candida parapsilosis Complex comprises three species, C. parapsilosis sensu stricto, C. metapsilosis and C. orthopsilosis, which have the same phenotypic characteristics, can be differentiated only by the genotype using PCR with restriction enzyme. The C. parapsilosis Complex is gaining prominence in the global epidemiology of candidiasis to be the second or third most isolated species, moreover, reports of resistance to some antifungal agents are worrying. Calcineurin molecule also responsible for resistance to antifungal drugs and thinking of new molecular targets with the objective of this study was to evaluate the potential synergistic antifungal and calcineurin inhibitor, cyclosporin A, against planktonic and biofilm forms of strains C. parapsilosis Complex from clinical sources. The susceptility assays with amphotericin B, fluconazole, voriconazole, caspofungin and cyclosporin A were performed by microdilution in accordance with the guidelines of the Clinical Laboratory Standards Institute. The method board in microdilution assay performed tests for synergism against planktonic cells of strains of C. parapsilosis Complex. Antifungal combinations formed by cyclosporin A were evaluated against biofilms forming and mature in polystyrene plates, where differences in the pattern of antifungal susceptibility among species were observed, but strains of C. parapsilosis sensu stricto were more sensitive to cyclosporin A to C. orthopsilosis and C. metapsilosis. Synergism between the antifungal and cyclosporin A was observed in strains of C. parapsilosis Complex. The combinations formed by antifungal and cyclosporin A were able to prevent the growth of the species in the planktonic phase of the complex, as well as in biofilm formation in CIM10X and CIM50X and showed inhibitory effect against mature biofilms of C. parapsilosis sensu stricto, C. metapsilosis and C. orthopsilosis in CIM50X. These results support the potential of inhibiting fungal calcineurin as a promising approach for increasing the efficiency of antifungal drugs.
| Identifer | oai:union.ndltd.org:IBICT/oai:www.teses.ufc.br:9398 |
| Date | 18 December 2013 |
| Creators | Ramila de Brito MacÃdo |
| Contributors | Rossana de Aguiar Cordeiro, Renato Evando Moreira Filho, Marcos FÃbio Gadelha Rocha |
| Publisher | Universidade Federal do CearÃ, Programa de PÃs-GraduaÃÃo em CiÃncias MÃdicas, UFC, BR |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Format | application/pdf |
| Source | reponame:Biblioteca Digital de Teses e Dissertações da UFC, instname:Universidade Federal do Ceará, instacron:UFC |
| Rights | info:eu-repo/semantics/openAccess |
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