Comportamento fenotípico e perfil de suscetibilidade de C. dubliniensis resistentes ao fluconazol frente a antifúngicos e associações
Autor(a) principal: | |
---|---|
Data de Publicação: | 2009 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Manancial - Repositório Digital da UFSM |
dARK ID: | ark:/26339/0013000016140 |
Texto Completo: | http://repositorio.ufsm.br/handle/1/5880 |
Resumo: | Widespread and prolonged usage of azoles in recent years has led to the rapid development of drug resistance in Candida species. In Candida albicans, resistance to fluconazole causes cross-resistance to other antifungals and an increase in virulence, making treatment still more difficult because of the limited therapeutical options. Nonetheless, other species has emerged as significant pathogens of clinical importance. Fluconazole resistance has been clinically described in Candida dubliniensis isolates and it is easily induced by in vitro exposure to the drug, but little is known about its consequences. In the present study, two groups of C. dubliniensis isolates were evaluated and compared in some points with the closely related species, C. albicans. One group was composed by fluconazole-susceptible clinical isolates and the other was composed by fluconazole-resistant laboratory derivatives from the former, in order to examine the changes on phenotypic characteristics and antifungal susceptibility accompanying the development of resistance to fluconazole. Resistant derivatives showed minimal inhibitory concentrations equal or higher than 64 μg/mL and proved to keep most of phenotypic characteristics that were tested before resistance was induced. However, some strains were not found to produce pseudomycelia and chlamydospores. Against killer toxins, C. dubliniensis did not present biotypes enough to permit its differentiation from C. albicans. On the other hand, when proteinase activity was evaluated, C. albicans activity was significantly higher than C. dubliniensis . Resistant derivatives of C. dubliniensis showed proteinase activity similar to fluconazole-susceptible isolates, suggesting that fluconazole resistance may not necessarily result on an increase of virulence in this species. Partial atmosphere of CO2, fluconazole at subinhibitory concentrations, or combination of both conditions, as well as addition of antiretrovirals on induction culture medium did not influence on proteinase activity of C. albicans and C. dubliniensis isolates. Finally, fluconazole-resistant isolates showed cross-resistance with ketoconazole, itraconazole, ravuconazole and terbinafine. In addition, associations of amphotericin B or terbinafine with azoles resulted mainly on indifferent interactions. On fluconazole-susceptible isolates, the most positive interaction came from association of amphotericin B with voriconazole. When resistance was induced, the best activity was found when terbinafine was combined with itraconazole. |
id |
UFSM_d1a23d556af33fc20a89f538ab879a70 |
---|---|
oai_identifier_str |
oai:repositorio.ufsm.br:1/5880 |
network_acronym_str |
UFSM |
network_name_str |
Manancial - Repositório Digital da UFSM |
repository_id_str |
|
spelling |
Comportamento fenotípico e perfil de suscetibilidade de C. dubliniensis resistentes ao fluconazol frente a antifúngicos e associaçõesCandida dubliniensisResistênciaFluconazolAntifúngicosCandida dubliniensisResistanceFluconazoleAntifungalsCNPQ::CIENCIAS DA SAUDE::FARMACIAWidespread and prolonged usage of azoles in recent years has led to the rapid development of drug resistance in Candida species. In Candida albicans, resistance to fluconazole causes cross-resistance to other antifungals and an increase in virulence, making treatment still more difficult because of the limited therapeutical options. Nonetheless, other species has emerged as significant pathogens of clinical importance. Fluconazole resistance has been clinically described in Candida dubliniensis isolates and it is easily induced by in vitro exposure to the drug, but little is known about its consequences. In the present study, two groups of C. dubliniensis isolates were evaluated and compared in some points with the closely related species, C. albicans. One group was composed by fluconazole-susceptible clinical isolates and the other was composed by fluconazole-resistant laboratory derivatives from the former, in order to examine the changes on phenotypic characteristics and antifungal susceptibility accompanying the development of resistance to fluconazole. Resistant derivatives showed minimal inhibitory concentrations equal or higher than 64 μg/mL and proved to keep most of phenotypic characteristics that were tested before resistance was induced. However, some strains were not found to produce pseudomycelia and chlamydospores. Against killer toxins, C. dubliniensis did not present biotypes enough to permit its differentiation from C. albicans. On the other hand, when proteinase activity was evaluated, C. albicans activity was significantly higher than C. dubliniensis . Resistant derivatives of C. dubliniensis showed proteinase activity similar to fluconazole-susceptible isolates, suggesting that fluconazole resistance may not necessarily result on an increase of virulence in this species. Partial atmosphere of CO2, fluconazole at subinhibitory concentrations, or combination of both conditions, as well as addition of antiretrovirals on induction culture medium did not influence on proteinase activity of C. albicans and C. dubliniensis isolates. Finally, fluconazole-resistant isolates showed cross-resistance with ketoconazole, itraconazole, ravuconazole and terbinafine. In addition, associations of amphotericin B or terbinafine with azoles resulted mainly on indifferent interactions. On fluconazole-susceptible isolates, the most positive interaction came from association of amphotericin B with voriconazole. When resistance was induced, the best activity was found when terbinafine was combined with itraconazole.Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorO uso prolongado e indiscriminado dos azólicos nos últimos anos permitiu um rápido desenvolvimento de resistência aos fármacos nas espécies de Candida. Em Candida albicans, a resistência ao fluconazol causa resistência cruzada a outros antifúngicos e aumento na virulência, tornando o tratamento ainda mais complicado por causa das opções terapêuticas limitadas. Ainda assim, outras espécies emergiram como patógenos significantes de importância clínica. A resistência ao fluconazol tem sido clinicamente descrita em isolados de Candida dubliniensis e é facilmente induzida pela exposição in vitro ao azólico, mas pouco se conhece sobre suas conseqüências. No presente estudo, dois grupos de isolados de C. dubliniensis foram avaliados e comparados em alguns aspectos com C. albicans. Um grupo era composto de isolados clínicos sensíveis ao fluconazol, e o outro, derivado do primeiro, era composto de isolados resistentes, com o intuito de analisar as alterações nas características fenotípicas e na suscetibilidade aos antifúngicos que acompanham o desenvolvimento de resistência ao fluconazol. Os derivados resistentes obtidos evidenciaram concentrações inibitórias mínimas maiores ou iguais a 64 μg/mL e mantiveram grande parte das características fenotípicas avaliadas anteriormente à indução da resistência. Entretanto, apenas o Ágar Suco de Tomate permitiu a identificação dessas estruturas em 100% dos isolados resistentes. Diante das toxinas killer , C. albicans e C. dubliniensis exibiram biotipos incapazes de permitir a diferenciação entre as espécies. Por outro lado, quando avaliada a atividade de proteinase, a de Candida albicans foi significativamente maior do que a de C. dubliniensis. Os derivados resistentes de C. dubliniensis evidenciaram atividade de proteinase semelhante a dos isolados sensíveis ao fluconazol, sugerindo que a resistência ao antifúngico pode não necessariamente acarretar aumento de virulência na espécie. Microaerofilia, fluconazol a concentrações subinibitórias, ou a combinação dessas duas condições, bem como a adição de anti-retrovirais ao meio de indução da enzima não exerceram influência sobre a atividade de proteinase em C. albicans e C. dubliniensis. C. dubliniensis resistentes ao fluconazol evidenciaram resistência cruzada com cetoconazol, itraconazol, ravuconazol e terbinafina. Em adição, as associações de anfotericina B ou terbinafina com azólicos resultaram principalmente em interações indiferentes. Em isolados sensíveis, a interação mais positiva resultou da associação de anfotericina B com voriconazol. Quando a resistência foi induzida, a melhor atividade foi encontrada quando a terbinafina foi combinada com itraconazol.Universidade Federal de Santa MariaBRFarmáciaUFSMPrograma de Pós-Graduação em Ciências FarmacêuticasAlves, Sydney Hartzhttp://lattes.cnpq.br/0330782478769631Santurio, Janio Moraishttp://lattes.cnpq.br/6316012260769979Burger, Marilise Escobarhttp://lattes.cnpq.br/9128090974948413Scheid, Liliane Alves2009-03-112009-03-112009-11-23info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfapplication/pdfSCHEID, Liliane Alves. COMPORTAMENTO FENOTÍPICO E PERFIL DE SUSCETIBILIDADE DE C. dubliniensis RESISTENTES AO FLUCONAZOL FRENTE A ANTIFÚNGICOS E ASSOCIAÇÕES. 2009. 112 f. Dissertação (Mestrado em Farmacologia) - Universidade Federal de Santa Maria, Santa Maria, 2009.http://repositorio.ufsm.br/handle/1/5880ark:/26339/0013000016140porinfo:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSM2022-10-19T17:59:42Zoai:repositorio.ufsm.br:1/5880Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2022-10-19T17:59:42Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.none.fl_str_mv |
Comportamento fenotípico e perfil de suscetibilidade de C. dubliniensis resistentes ao fluconazol frente a antifúngicos e associações |
title |
Comportamento fenotípico e perfil de suscetibilidade de C. dubliniensis resistentes ao fluconazol frente a antifúngicos e associações |
spellingShingle |
Comportamento fenotípico e perfil de suscetibilidade de C. dubliniensis resistentes ao fluconazol frente a antifúngicos e associações Scheid, Liliane Alves Candida dubliniensis Resistência Fluconazol Antifúngicos Candida dubliniensis Resistance Fluconazole Antifungals CNPQ::CIENCIAS DA SAUDE::FARMACIA |
title_short |
Comportamento fenotípico e perfil de suscetibilidade de C. dubliniensis resistentes ao fluconazol frente a antifúngicos e associações |
title_full |
Comportamento fenotípico e perfil de suscetibilidade de C. dubliniensis resistentes ao fluconazol frente a antifúngicos e associações |
title_fullStr |
Comportamento fenotípico e perfil de suscetibilidade de C. dubliniensis resistentes ao fluconazol frente a antifúngicos e associações |
title_full_unstemmed |
Comportamento fenotípico e perfil de suscetibilidade de C. dubliniensis resistentes ao fluconazol frente a antifúngicos e associações |
title_sort |
Comportamento fenotípico e perfil de suscetibilidade de C. dubliniensis resistentes ao fluconazol frente a antifúngicos e associações |
author |
Scheid, Liliane Alves |
author_facet |
Scheid, Liliane Alves |
author_role |
author |
dc.contributor.none.fl_str_mv |
Alves, Sydney Hartz http://lattes.cnpq.br/0330782478769631 Santurio, Janio Morais http://lattes.cnpq.br/6316012260769979 Burger, Marilise Escobar http://lattes.cnpq.br/9128090974948413 |
dc.contributor.author.fl_str_mv |
Scheid, Liliane Alves |
dc.subject.por.fl_str_mv |
Candida dubliniensis Resistência Fluconazol Antifúngicos Candida dubliniensis Resistance Fluconazole Antifungals CNPQ::CIENCIAS DA SAUDE::FARMACIA |
topic |
Candida dubliniensis Resistência Fluconazol Antifúngicos Candida dubliniensis Resistance Fluconazole Antifungals CNPQ::CIENCIAS DA SAUDE::FARMACIA |
description |
Widespread and prolonged usage of azoles in recent years has led to the rapid development of drug resistance in Candida species. In Candida albicans, resistance to fluconazole causes cross-resistance to other antifungals and an increase in virulence, making treatment still more difficult because of the limited therapeutical options. Nonetheless, other species has emerged as significant pathogens of clinical importance. Fluconazole resistance has been clinically described in Candida dubliniensis isolates and it is easily induced by in vitro exposure to the drug, but little is known about its consequences. In the present study, two groups of C. dubliniensis isolates were evaluated and compared in some points with the closely related species, C. albicans. One group was composed by fluconazole-susceptible clinical isolates and the other was composed by fluconazole-resistant laboratory derivatives from the former, in order to examine the changes on phenotypic characteristics and antifungal susceptibility accompanying the development of resistance to fluconazole. Resistant derivatives showed minimal inhibitory concentrations equal or higher than 64 μg/mL and proved to keep most of phenotypic characteristics that were tested before resistance was induced. However, some strains were not found to produce pseudomycelia and chlamydospores. Against killer toxins, C. dubliniensis did not present biotypes enough to permit its differentiation from C. albicans. On the other hand, when proteinase activity was evaluated, C. albicans activity was significantly higher than C. dubliniensis . Resistant derivatives of C. dubliniensis showed proteinase activity similar to fluconazole-susceptible isolates, suggesting that fluconazole resistance may not necessarily result on an increase of virulence in this species. Partial atmosphere of CO2, fluconazole at subinhibitory concentrations, or combination of both conditions, as well as addition of antiretrovirals on induction culture medium did not influence on proteinase activity of C. albicans and C. dubliniensis isolates. Finally, fluconazole-resistant isolates showed cross-resistance with ketoconazole, itraconazole, ravuconazole and terbinafine. In addition, associations of amphotericin B or terbinafine with azoles resulted mainly on indifferent interactions. On fluconazole-susceptible isolates, the most positive interaction came from association of amphotericin B with voriconazole. When resistance was induced, the best activity was found when terbinafine was combined with itraconazole. |
publishDate |
2009 |
dc.date.none.fl_str_mv |
2009-03-11 2009-03-11 2009-11-23 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
SCHEID, Liliane Alves. COMPORTAMENTO FENOTÍPICO E PERFIL DE SUSCETIBILIDADE DE C. dubliniensis RESISTENTES AO FLUCONAZOL FRENTE A ANTIFÚNGICOS E ASSOCIAÇÕES. 2009. 112 f. Dissertação (Mestrado em Farmacologia) - Universidade Federal de Santa Maria, Santa Maria, 2009. http://repositorio.ufsm.br/handle/1/5880 |
dc.identifier.dark.fl_str_mv |
ark:/26339/0013000016140 |
identifier_str_mv |
SCHEID, Liliane Alves. COMPORTAMENTO FENOTÍPICO E PERFIL DE SUSCETIBILIDADE DE C. dubliniensis RESISTENTES AO FLUCONAZOL FRENTE A ANTIFÚNGICOS E ASSOCIAÇÕES. 2009. 112 f. Dissertação (Mestrado em Farmacologia) - Universidade Federal de Santa Maria, Santa Maria, 2009. ark:/26339/0013000016140 |
url |
http://repositorio.ufsm.br/handle/1/5880 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria BR Farmácia UFSM Programa de Pós-Graduação em Ciências Farmacêuticas |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria BR Farmácia UFSM Programa de Pós-Graduação em Ciências Farmacêuticas |
dc.source.none.fl_str_mv |
reponame:Manancial - Repositório Digital da UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
instname_str |
Universidade Federal de Santa Maria (UFSM) |
instacron_str |
UFSM |
institution |
UFSM |
reponame_str |
Manancial - Repositório Digital da UFSM |
collection |
Manancial - Repositório Digital da UFSM |
repository.name.fl_str_mv |
Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
atendimento.sib@ufsm.br||tedebc@gmail.com |
_version_ |
1821326202619559936 |