Insights into the multi-azole resistance profile in Candida haemulonii species complex
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRGS |
Texto Completo: | http://hdl.handle.net/10183/267849 |
Resumo: | The Candida haemulonii complex (C. duobushaemulonii, C. haemulonii, and C. haemulonii var. vulnera) is composed of emerging, opportunistic human fungal pathogens able to cause invasive infections with high rates of clinical treatment failure. This fungal complex typically demonstrates resistance to first-line antifungals, including fluconazole. In the present work, we have investigated the azole resistance mechanisms expressed in Brazilian clinical isolates forming the C. haemulonii complex. Initially, 12 isolates were subjected to an antifungal susceptibility test, and azole cross-resistance was detected in almost all isolates (91.7%). In order to understand the azole resistance mechanistic basis, the efflux pump activity was assessed by rhodamine-6G. The C. haemulonii complex exhibited a significantly higher rhodamine-6G efflux than the other non-albicans Candida species tested (C. tropicalis, C. krusei, and C. lusitaneae). Notably, the efflux pump inhibitors (Phe-Arg and FK506) reversed the fluconazole and voricolazole resistance phenotypes in the C. haemulonii species complex. Expression analysis indicated that the efflux pump (ChCDR1, ChCDR2, and ChMDR1) and ERG11 genes were not modulated by either fluconazole or voriconazole treatments. Further, ERG11 gene sequencing revealed several mutations, some of which culminated in amino acid polymorphisms, as previously reported in azole-resistant Candida spp. Collectively, these data point out the relevance of drug efflux pumps in mediating azole resistance in the C. haemulonii complex, and mutations in ERG11p may contribute to this resistance profile. |
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Silva, Laura NunesRamos, Lívia de SouzaOliveira, Simone Santiago CarvalhoMagalhães, Lucas BarrosSquizani, Eamim DaidrêSilva, Lívia Kmetzsch Rosa eVainstein, Marilene HenningSá, Marta Helena Branquinha deSantos, André Luis Souza dos2023-11-30T03:24:32Z20202309-608Xhttp://hdl.handle.net/10183/267849001172767The Candida haemulonii complex (C. duobushaemulonii, C. haemulonii, and C. haemulonii var. vulnera) is composed of emerging, opportunistic human fungal pathogens able to cause invasive infections with high rates of clinical treatment failure. This fungal complex typically demonstrates resistance to first-line antifungals, including fluconazole. In the present work, we have investigated the azole resistance mechanisms expressed in Brazilian clinical isolates forming the C. haemulonii complex. Initially, 12 isolates were subjected to an antifungal susceptibility test, and azole cross-resistance was detected in almost all isolates (91.7%). In order to understand the azole resistance mechanistic basis, the efflux pump activity was assessed by rhodamine-6G. The C. haemulonii complex exhibited a significantly higher rhodamine-6G efflux than the other non-albicans Candida species tested (C. tropicalis, C. krusei, and C. lusitaneae). Notably, the efflux pump inhibitors (Phe-Arg and FK506) reversed the fluconazole and voricolazole resistance phenotypes in the C. haemulonii species complex. Expression analysis indicated that the efflux pump (ChCDR1, ChCDR2, and ChMDR1) and ERG11 genes were not modulated by either fluconazole or voriconazole treatments. Further, ERG11 gene sequencing revealed several mutations, some of which culminated in amino acid polymorphisms, as previously reported in azole-resistant Candida spp. Collectively, these data point out the relevance of drug efflux pumps in mediating azole resistance in the C. haemulonii complex, and mutations in ERG11p may contribute to this resistance profile.application/pdfengJournal of fungi. Basel. Vol. 6, n. 4 (Dec. 2020), e215, pFluconazolCandidaVoriconazolAzole resistanceEfflux pumpsLanosterol 14α-demethylaseNon-albicans Candida speciesInsights into the multi-azole resistance profile in Candida haemulonii species complexEstrangeiroinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSTEXT001172767.pdf.txt001172767.pdf.txtExtracted Texttext/plain61335http://www.lume.ufrgs.br/bitstream/10183/267849/2/001172767.pdf.txt8930756314ddee4aaea7509cfcc664bbMD52ORIGINAL001172767.pdfTexto completo (inglês)application/pdf2080603http://www.lume.ufrgs.br/bitstream/10183/267849/1/001172767.pdf3d305a772488df8622c20a1eada6248aMD5110183/2678492023-12-06 04:25:27.533525oai:www.lume.ufrgs.br:10183/267849Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2023-12-06T06:25:27Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false |
dc.title.pt_BR.fl_str_mv |
Insights into the multi-azole resistance profile in Candida haemulonii species complex |
title |
Insights into the multi-azole resistance profile in Candida haemulonii species complex |
spellingShingle |
Insights into the multi-azole resistance profile in Candida haemulonii species complex Silva, Laura Nunes Fluconazol Candida Voriconazol Azole resistance Efflux pumps Lanosterol 14α-demethylase Non-albicans Candida species |
title_short |
Insights into the multi-azole resistance profile in Candida haemulonii species complex |
title_full |
Insights into the multi-azole resistance profile in Candida haemulonii species complex |
title_fullStr |
Insights into the multi-azole resistance profile in Candida haemulonii species complex |
title_full_unstemmed |
Insights into the multi-azole resistance profile in Candida haemulonii species complex |
title_sort |
Insights into the multi-azole resistance profile in Candida haemulonii species complex |
author |
Silva, Laura Nunes |
author_facet |
Silva, Laura Nunes Ramos, Lívia de Souza Oliveira, Simone Santiago Carvalho Magalhães, Lucas Barros Squizani, Eamim Daidrê Silva, Lívia Kmetzsch Rosa e Vainstein, Marilene Henning Sá, Marta Helena Branquinha de Santos, André Luis Souza dos |
author_role |
author |
author2 |
Ramos, Lívia de Souza Oliveira, Simone Santiago Carvalho Magalhães, Lucas Barros Squizani, Eamim Daidrê Silva, Lívia Kmetzsch Rosa e Vainstein, Marilene Henning Sá, Marta Helena Branquinha de Santos, André Luis Souza dos |
author2_role |
author author author author author author author author |
dc.contributor.author.fl_str_mv |
Silva, Laura Nunes Ramos, Lívia de Souza Oliveira, Simone Santiago Carvalho Magalhães, Lucas Barros Squizani, Eamim Daidrê Silva, Lívia Kmetzsch Rosa e Vainstein, Marilene Henning Sá, Marta Helena Branquinha de Santos, André Luis Souza dos |
dc.subject.por.fl_str_mv |
Fluconazol Candida Voriconazol |
topic |
Fluconazol Candida Voriconazol Azole resistance Efflux pumps Lanosterol 14α-demethylase Non-albicans Candida species |
dc.subject.eng.fl_str_mv |
Azole resistance Efflux pumps Lanosterol 14α-demethylase Non-albicans Candida species |
description |
The Candida haemulonii complex (C. duobushaemulonii, C. haemulonii, and C. haemulonii var. vulnera) is composed of emerging, opportunistic human fungal pathogens able to cause invasive infections with high rates of clinical treatment failure. This fungal complex typically demonstrates resistance to first-line antifungals, including fluconazole. In the present work, we have investigated the azole resistance mechanisms expressed in Brazilian clinical isolates forming the C. haemulonii complex. Initially, 12 isolates were subjected to an antifungal susceptibility test, and azole cross-resistance was detected in almost all isolates (91.7%). In order to understand the azole resistance mechanistic basis, the efflux pump activity was assessed by rhodamine-6G. The C. haemulonii complex exhibited a significantly higher rhodamine-6G efflux than the other non-albicans Candida species tested (C. tropicalis, C. krusei, and C. lusitaneae). Notably, the efflux pump inhibitors (Phe-Arg and FK506) reversed the fluconazole and voricolazole resistance phenotypes in the C. haemulonii species complex. Expression analysis indicated that the efflux pump (ChCDR1, ChCDR2, and ChMDR1) and ERG11 genes were not modulated by either fluconazole or voriconazole treatments. Further, ERG11 gene sequencing revealed several mutations, some of which culminated in amino acid polymorphisms, as previously reported in azole-resistant Candida spp. Collectively, these data point out the relevance of drug efflux pumps in mediating azole resistance in the C. haemulonii complex, and mutations in ERG11p may contribute to this resistance profile. |
publishDate |
2020 |
dc.date.issued.fl_str_mv |
2020 |
dc.date.accessioned.fl_str_mv |
2023-11-30T03:24:32Z |
dc.type.driver.fl_str_mv |
Estrangeiro info:eu-repo/semantics/article |
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info:eu-repo/semantics/publishedVersion |
format |
article |
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publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10183/267849 |
dc.identifier.issn.pt_BR.fl_str_mv |
2309-608X |
dc.identifier.nrb.pt_BR.fl_str_mv |
001172767 |
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2309-608X 001172767 |
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http://hdl.handle.net/10183/267849 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.pt_BR.fl_str_mv |
Journal of fungi. Basel. Vol. 6, n. 4 (Dec. 2020), e215, p |
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info:eu-repo/semantics/openAccess |
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openAccess |
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