Atividade in vitro Anti-Pythium insidiosum do cloridrato de amorolfina e azitromicina isoladamente e em combinação
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Repositório Institucional Manancial UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/21065 |
Resumo: | Pythium insidiosum, belonging to the Kingdom Stramenopila (super group Stramenopiles- Alveolata-Rhizaria - SAR), Class Oomycetes, Order Pythiales, Family Pythiaceae, Genus Pythium and Species Pythium insidiosum is the etiological agent of pythiosis, a chronic granulomatous disease, usually fatal, capable of infecting animals and humans. It is occurring in tropical, subtropical, and temperate areas. Pythiosis is commonly reported in humans in Southeast Asia, mainly in Thailand. Conversely, in Brazil, pythiosis affects mostly equines and it is more prevalent in Pantanal Mato-Grossense and Rio Grande do Sul. This oomycete has characteristics that distinguish it from fungi, especially the incomplete ergosterol biosynthesis pathway, the main target of action of existing antifungal drugs, making it less susceptible to commercially available chemotherapeutic therapies. In an attempt to establish an efficient therapeutic protocol for the control of this disease, therapeutic possibilities to combat infections by P. insidiosum have been widely evaluated. Thus, this study evaluated the in vitro susceptibility profile of P. insidiosum isolates (n = 20) against amorolfine hydrochloride (AMR) and azithromycin (AZM) alone and in combination. The susceptibility tests were performed according to CLSI protocol M38-A2 and the combinations were evaluated by the checkerboard microdilution method. In addition, scanning electron microscopy and transmittance were performed in order to verify the effects on the isolates treated with the drugs. All P. insidiosum isolates evaluated showed minimum inhibitory concentration (MIC) ranging from 16 to 64 mg/L when using AMR and from 8 to 64 mg/L for AZM. Synergistic interactions were not observed, showing 59.8% antagonism and 36.2% indifferent interactions. The scanning electron microscopy and transmittance analyzes showed changes in the surface of the hyphae of P. insidiosum, disorganization of the intracellular organelles, as well as changes in the plasma membrane and cell wall when the microorganism was treated with both drugs. The use of drugs alone presented significant therapeutic potential for the treatment of pythiosis. This is the first study to demonstrate the in vitro activity of AMR, as well as to evaluate its combination with AZM against P. insidiosum. Thus, this drug may represent a therapeutic potential to be further investigated against cutaneous and subcutaneous forms of pythiosis. |
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2021-06-07T18:38:43Z2021-06-07T18:38:43Z2020-08-28http://repositorio.ufsm.br/handle/1/21065Pythium insidiosum, belonging to the Kingdom Stramenopila (super group Stramenopiles- Alveolata-Rhizaria - SAR), Class Oomycetes, Order Pythiales, Family Pythiaceae, Genus Pythium and Species Pythium insidiosum is the etiological agent of pythiosis, a chronic granulomatous disease, usually fatal, capable of infecting animals and humans. It is occurring in tropical, subtropical, and temperate areas. Pythiosis is commonly reported in humans in Southeast Asia, mainly in Thailand. Conversely, in Brazil, pythiosis affects mostly equines and it is more prevalent in Pantanal Mato-Grossense and Rio Grande do Sul. This oomycete has characteristics that distinguish it from fungi, especially the incomplete ergosterol biosynthesis pathway, the main target of action of existing antifungal drugs, making it less susceptible to commercially available chemotherapeutic therapies. In an attempt to establish an efficient therapeutic protocol for the control of this disease, therapeutic possibilities to combat infections by P. insidiosum have been widely evaluated. Thus, this study evaluated the in vitro susceptibility profile of P. insidiosum isolates (n = 20) against amorolfine hydrochloride (AMR) and azithromycin (AZM) alone and in combination. The susceptibility tests were performed according to CLSI protocol M38-A2 and the combinations were evaluated by the checkerboard microdilution method. In addition, scanning electron microscopy and transmittance were performed in order to verify the effects on the isolates treated with the drugs. All P. insidiosum isolates evaluated showed minimum inhibitory concentration (MIC) ranging from 16 to 64 mg/L when using AMR and from 8 to 64 mg/L for AZM. Synergistic interactions were not observed, showing 59.8% antagonism and 36.2% indifferent interactions. The scanning electron microscopy and transmittance analyzes showed changes in the surface of the hyphae of P. insidiosum, disorganization of the intracellular organelles, as well as changes in the plasma membrane and cell wall when the microorganism was treated with both drugs. The use of drugs alone presented significant therapeutic potential for the treatment of pythiosis. This is the first study to demonstrate the in vitro activity of AMR, as well as to evaluate its combination with AZM against P. insidiosum. Thus, this drug may represent a therapeutic potential to be further investigated against cutaneous and subcutaneous forms of pythiosis.Pythium insidiosum, pertence ao Reino Stramenopila (super grupo Stramenopiles-Alveolata- Rhizaria - SAR), Classe Oomycetes, Ordem Pythiales, Família Pythiaceae, Gênero Pythium e Espécie Pythium insidiosum é o agente etiológico da pitiose, doença granulomatosa crônica, geralmente fatal, com capacidade de infectar animais e seres humanos. Prevalente em áreas tropicais, subtropicais e temperadas, a pitiose é comumente relatada em seres humanos no sudeste da Ásia, principalmente na Tailândia. Entretanto, no Brasil, a pitiose tem maior ocorrência no Pantanal Mato-Grossense e no Rio Grande do Sul, sendo a espécie equina a mais acometida. Este oomiceto apresenta características que o distingue dos fungos, especialmente a via de biossíntese de ergosterol incompleta, principal alvo de ação de fármacos antifúngicos existentes, tornando-o pouco suscetível as terapias quimioterápicas comercialmente disponíveis. Na tentativa de estabelecer um protocolo terapêutico eficiente para o controle desta enfermidade, possibilidades terapêuticas visando combater infecções por P. insidiosum vêm sendo amplamente avaliadas. Sendo assim, este estudo, avaliou o perfil de suscetibilidade in vitro de isolados de P. insidiosum (n = 20) frente ao cloridrato de amorolfina (AMR) e à azitromicina (AZM) isoladamente e em combinação. Os testes de suscetibilidade foram realizados de acordo com protocolo M38-A2 do CLSI e as combinações foram avaliadas pelo método de microdiluição checkerboard. Adicionalmente, realizou-se microscopia eletrônica de varredura e transmitância a fim de verificar os efeitos sobre os isolados tratados com os fármacos. Todos os isolados de P. insidiosum avaliados apresentaram concentração inibitória mínima (CIMs) variando de 16 a 64 mg/L quando utilizado AMR e de 8 a 64 mg/L para AZM. Interações sinérgicas não foram observadas, evidenciando-se 59,8% de antagonismo e 36,2% de interações indiferentes. Nas análises de microscopia eletrônica de varredura e transmitância, evidenciou-se alterações na superfície das hifas de P. insidiosum, desorganização das organelas intracelulares, bem como modificações na membrana plasmática e na parede celular quando o micro-organismo foi tratado com ambos os fármacos. O uso dos fármacos isoladamente apresentou um potencial terapêutico significativo para o tratamento da pitiose. Este é o primeiro estudo a demonstrar a atividade in vitro da AMR, bem como avaliar sua combinação com AZM frente a P. insidiosum. Desta forma, este fármaco pode representar um potencial terapêutico a ser futuramente pesquisado contra formas cutâneas e subcutâneas de pitiose.porUniversidade Federal de Santa MariaCentro de Ciências da SaúdePrograma de Pós-Graduação em Ciências FarmacêuticasUFSMBrasilFarmáciaAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessOomicetoPitioseSuscetibilidadeAmorolfinaAzitromicinaTratamentoOomycetePythiosisSusceptibilityAmorolfineAzithromycinTreatmentCNPQ::CIENCIAS DA SAUDE::FARMACIAAtividade in vitro Anti-Pythium insidiosum do cloridrato de amorolfina e azitromicina isoladamente e em combinaçãoIn vitro Anti-Pythium insidiosum activity of amorolfine hydrochloride and azithromycin, alone and in combinationinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisBotton, Sônia de Avilahttp://lattes.cnpq.br/1177504021154172Pereira, Daniela Isabel BrayerWeiblen, CarlaIaniski, Lara Baccarin400300000005600f465ec0c-6e20-4b5a-8cd6-3f58965068577442d295-dfc1-4749-b19d-3f3a1a3bd6968cf0f648-751e-463b-8607-0f38cce0874cea989878-b508-4854-8507-2d960a878234reponame:Repositório Institucional Manancial UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALDIS_PPGCF_2020_IANISKI_LARA.pdfDIS_PPGCF_2020_IANISKI_LARA.pdfDissertação de Mestradoapplication/pdf1810323http://repositorio.ufsm.br/bitstream/1/21065/1/DIS_PPGCF_2020_IANISKI_LARA.pdf5916387ddefb97fbdf288c300d8f7a61MD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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dc.title.por.fl_str_mv |
Atividade in vitro Anti-Pythium insidiosum do cloridrato de amorolfina e azitromicina isoladamente e em combinação |
dc.title.alternative.eng.fl_str_mv |
In vitro Anti-Pythium insidiosum activity of amorolfine hydrochloride and azithromycin, alone and in combination |
title |
Atividade in vitro Anti-Pythium insidiosum do cloridrato de amorolfina e azitromicina isoladamente e em combinação |
spellingShingle |
Atividade in vitro Anti-Pythium insidiosum do cloridrato de amorolfina e azitromicina isoladamente e em combinação Ianiski, Lara Baccarin Oomiceto Pitiose Suscetibilidade Amorolfina Azitromicina Tratamento Oomycete Pythiosis Susceptibility Amorolfine Azithromycin Treatment CNPQ::CIENCIAS DA SAUDE::FARMACIA |
title_short |
Atividade in vitro Anti-Pythium insidiosum do cloridrato de amorolfina e azitromicina isoladamente e em combinação |
title_full |
Atividade in vitro Anti-Pythium insidiosum do cloridrato de amorolfina e azitromicina isoladamente e em combinação |
title_fullStr |
Atividade in vitro Anti-Pythium insidiosum do cloridrato de amorolfina e azitromicina isoladamente e em combinação |
title_full_unstemmed |
Atividade in vitro Anti-Pythium insidiosum do cloridrato de amorolfina e azitromicina isoladamente e em combinação |
title_sort |
Atividade in vitro Anti-Pythium insidiosum do cloridrato de amorolfina e azitromicina isoladamente e em combinação |
author |
Ianiski, Lara Baccarin |
author_facet |
Ianiski, Lara Baccarin |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Botton, Sônia de Avila |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/1177504021154172 |
dc.contributor.referee1.fl_str_mv |
Pereira, Daniela Isabel Brayer |
dc.contributor.referee2.fl_str_mv |
Weiblen, Carla |
dc.contributor.author.fl_str_mv |
Ianiski, Lara Baccarin |
contributor_str_mv |
Botton, Sônia de Avila Pereira, Daniela Isabel Brayer Weiblen, Carla |
dc.subject.por.fl_str_mv |
Oomiceto Pitiose Suscetibilidade Amorolfina Azitromicina Tratamento |
topic |
Oomiceto Pitiose Suscetibilidade Amorolfina Azitromicina Tratamento Oomycete Pythiosis Susceptibility Amorolfine Azithromycin Treatment CNPQ::CIENCIAS DA SAUDE::FARMACIA |
dc.subject.eng.fl_str_mv |
Oomycete Pythiosis Susceptibility Amorolfine Azithromycin Treatment |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS DA SAUDE::FARMACIA |
description |
Pythium insidiosum, belonging to the Kingdom Stramenopila (super group Stramenopiles- Alveolata-Rhizaria - SAR), Class Oomycetes, Order Pythiales, Family Pythiaceae, Genus Pythium and Species Pythium insidiosum is the etiological agent of pythiosis, a chronic granulomatous disease, usually fatal, capable of infecting animals and humans. It is occurring in tropical, subtropical, and temperate areas. Pythiosis is commonly reported in humans in Southeast Asia, mainly in Thailand. Conversely, in Brazil, pythiosis affects mostly equines and it is more prevalent in Pantanal Mato-Grossense and Rio Grande do Sul. This oomycete has characteristics that distinguish it from fungi, especially the incomplete ergosterol biosynthesis pathway, the main target of action of existing antifungal drugs, making it less susceptible to commercially available chemotherapeutic therapies. In an attempt to establish an efficient therapeutic protocol for the control of this disease, therapeutic possibilities to combat infections by P. insidiosum have been widely evaluated. Thus, this study evaluated the in vitro susceptibility profile of P. insidiosum isolates (n = 20) against amorolfine hydrochloride (AMR) and azithromycin (AZM) alone and in combination. The susceptibility tests were performed according to CLSI protocol M38-A2 and the combinations were evaluated by the checkerboard microdilution method. In addition, scanning electron microscopy and transmittance were performed in order to verify the effects on the isolates treated with the drugs. All P. insidiosum isolates evaluated showed minimum inhibitory concentration (MIC) ranging from 16 to 64 mg/L when using AMR and from 8 to 64 mg/L for AZM. Synergistic interactions were not observed, showing 59.8% antagonism and 36.2% indifferent interactions. The scanning electron microscopy and transmittance analyzes showed changes in the surface of the hyphae of P. insidiosum, disorganization of the intracellular organelles, as well as changes in the plasma membrane and cell wall when the microorganism was treated with both drugs. The use of drugs alone presented significant therapeutic potential for the treatment of pythiosis. This is the first study to demonstrate the in vitro activity of AMR, as well as to evaluate its combination with AZM against P. insidiosum. Thus, this drug may represent a therapeutic potential to be further investigated against cutaneous and subcutaneous forms of pythiosis. |
publishDate |
2020 |
dc.date.issued.fl_str_mv |
2020-08-28 |
dc.date.accessioned.fl_str_mv |
2021-06-07T18:38:43Z |
dc.date.available.fl_str_mv |
2021-06-07T18:38:43Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/masterThesis |
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masterThesis |
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http://repositorio.ufsm.br/handle/1/21065 |
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http://repositorio.ufsm.br/handle/1/21065 |
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por |
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por |
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400300000005 |
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600 |
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Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
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Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências da Saúde |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Ciências Farmacêuticas |
dc.publisher.initials.fl_str_mv |
UFSM |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Farmácia |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências da Saúde |
dc.source.none.fl_str_mv |
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