Fotoinativação de micobactérias de crescimento rápido por porfirinas tetra-catiônicas
Autor(a) principal: | |
---|---|
Data de Publicação: | 2023 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Repositório Institucional Manancial UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/28301 |
Resumo: | Antimicrobial Photodynamic Inactivation (aPDI) is an emerging non-invasive treatment that involves the use of a photosensitizer (PS), light and molecular oxygen to inactivate microorganisms. Thus, the application of aPDI has been gaining prominence in the field of microbiology, especially in the treatment of infections that persist after conventional antibiotic therapy. In this scenario are included mycobacterioses, because they do not have many therapeutic options available and they require a slow treatment, thus being promising targets of aPDI. The objective of this work is to explore the action of neutral (4-TPyP and 3- TPyP) and tetra-cationic porphyrins, with peripheral complexes of platinum(II) (3-PtTPyP/4- PtTPyP) and palladium(II) (3-PdTPyP/4-PdTPyP), on Rapidly Growing Mycobacteria (RGM) strains that cause skin and mucous infections. In this study were used standard strains of Mycobacteroides abscessus subsp. abscessus (ATCC 19977), Mycobacteroides abscessus subsp. massiliense (ATCC 48898), Mycolicibacterium fortuitum (ATCC 6841), and Mycolicibacterium smegmatis (ATCC 700084). For this purpose, the susceptibility of microorganisms in the planktonic form was obtained through conventional microdilution techniques and by the time-kill curve. The determination of possible reactive oxygen species (ROS) produced by the PS was carried out using compounds that scavenge these reactive species. The impact of these porphyrins on the mycobacterial surface can be visualized and analyzed through images obtained by the Atomic Force Microscopy (AFM) technique. The results demonstrated the significant antimicrobial activity of the studied porphyrins, with emphasis on the meta substituted isomer 3-PtTPyP and 3-PdTPyP. Furthermore, singlet oxygen (¹O2) was the main reactive species detected, being attributed to it the predominant activity in photo-oxidative damages. Finally, the bactericidal activity of Pt(II) and Pd(II) porphyrins was proven in two irradiation sessions, and the AFM images demonstrate the aggression of these porphyrins on the bacterial cell wall, also their influence on nanomechanical adhesion and electrostatic properties. Therefore, porphyrins are a useful and promising tool to eradicate RGM directly via remote control of light irradiation. The impact and scientific contribution of this work are based on the discovery of a potential new therapeutic approach against cutaneous mycobacterial infections and, in addition, they stimulate the deepening of methodologies that aim at the insertion of porphyrins as a new antimicrobial agent. |
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2023-03-20T20:03:07Z2023-03-20T20:03:07Z2023-01-23http://repositorio.ufsm.br/handle/1/28301Antimicrobial Photodynamic Inactivation (aPDI) is an emerging non-invasive treatment that involves the use of a photosensitizer (PS), light and molecular oxygen to inactivate microorganisms. Thus, the application of aPDI has been gaining prominence in the field of microbiology, especially in the treatment of infections that persist after conventional antibiotic therapy. In this scenario are included mycobacterioses, because they do not have many therapeutic options available and they require a slow treatment, thus being promising targets of aPDI. The objective of this work is to explore the action of neutral (4-TPyP and 3- TPyP) and tetra-cationic porphyrins, with peripheral complexes of platinum(II) (3-PtTPyP/4- PtTPyP) and palladium(II) (3-PdTPyP/4-PdTPyP), on Rapidly Growing Mycobacteria (RGM) strains that cause skin and mucous infections. In this study were used standard strains of Mycobacteroides abscessus subsp. abscessus (ATCC 19977), Mycobacteroides abscessus subsp. massiliense (ATCC 48898), Mycolicibacterium fortuitum (ATCC 6841), and Mycolicibacterium smegmatis (ATCC 700084). For this purpose, the susceptibility of microorganisms in the planktonic form was obtained through conventional microdilution techniques and by the time-kill curve. The determination of possible reactive oxygen species (ROS) produced by the PS was carried out using compounds that scavenge these reactive species. The impact of these porphyrins on the mycobacterial surface can be visualized and analyzed through images obtained by the Atomic Force Microscopy (AFM) technique. The results demonstrated the significant antimicrobial activity of the studied porphyrins, with emphasis on the meta substituted isomer 3-PtTPyP and 3-PdTPyP. Furthermore, singlet oxygen (¹O2) was the main reactive species detected, being attributed to it the predominant activity in photo-oxidative damages. Finally, the bactericidal activity of Pt(II) and Pd(II) porphyrins was proven in two irradiation sessions, and the AFM images demonstrate the aggression of these porphyrins on the bacterial cell wall, also their influence on nanomechanical adhesion and electrostatic properties. Therefore, porphyrins are a useful and promising tool to eradicate RGM directly via remote control of light irradiation. The impact and scientific contribution of this work are based on the discovery of a potential new therapeutic approach against cutaneous mycobacterial infections and, in addition, they stimulate the deepening of methodologies that aim at the insertion of porphyrins as a new antimicrobial agent.A Terapia de Fotoinativação Antimicrobiana (TFIa) é uma modalidade emergente de tratamento não invasiva, que envolve o uso de um fotossensibilizador (FS), luz e oxigênio molecular para inativar microrganismos. Dessa forma, a aplicação da TFIa vem ganhando destaque no campo da microbiologia especialmente no tratamento de infecções que persistem após a antibióticoterapia convencional. Neste cenário, incluem-se as micobacterioses que, por não possuírem muitas opções terapêuticas disponíveis e por necessitarem de um tratamento lento, constituem, alvos promissores da TFIa. Desse modo, o objetivo deste trabalho é explorar a ação de porfirinas neutras (4-TPyP e 3-TPyP) e tetra-catiônicas, com complexos periféricos de platina(II) (3-PtTPyP/4-PtTPyP) e paládio(II) (3-PdTPyP/4-PdTPyP), sobre cepas de Micobactérias de Crescimento Rápido (MCR) causadoras de infecções de pele e mucosas. Neste estudo foram utilizadas cepas padrão de Mycobacteroides abscessus subsp. abscessus (ATCC 19977), Mycobacteroides abscessus subsp. massiliense (ATCC 48898), Mycolicibacterium fortuitum (ATCC 6841) e Mycolicibacterium smegmatis (ATCC 700084). Para tanto, a suscetibilidade dos microrganismos na forma planctônica foi obtida através de técnicas convencionais de microdiluição e pelo ensaio de curva de morte. A determinação de possíveis espécies reativas de oxigênio (EROs) produzidas pelos FS foi realizada utilizandose compostos sequestradores destas espécies reativas. O impacto dessas porfirinas na superfície micobacteriana pode ser visualizado e analisado através das imagens obtidas pela técnica de Microscopia de Força Atômica (MFA). Os resultados demostraram a significativa atividade antimicrobiana das porfirinas em estudo, com destaque para os isômeros metasubstituídos 3-PtTPyP e 3-PdTPyP. Ademais, o oxigênio singlete (¹O2) foi a principal espécie reativa detectada, sendo atribuída a ela a atividade predominante nos danos fotooxidativos. Por fim, a atividade bactericida de porfirinas de Pt(II) e Pd(II) foi comprovada em duas sessões de irradiação e as imagens da MFA demonstram a agressão dessas porfirinas na parede celular bacteriana, além da sua influência nas propriedades de adesão nano-mecânicas e eletrostáticas. Sendo assim, as porfirinas apresentaram-se como uma ferramenta útil e promissora para erradicar MCR diretamente pelo controle remoto da irradiação de luz. O impacto e contribuição científica deste trabalho estão alicerçados na descoberta de uma potencial nova abordagem terapêutica contra infecções micobacterianas cutâneas e, além disso, estimulam o aprofundamento em metodologias que visem a inserção das porfirinas como um novo agente antimicrobiano.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESporUniversidade Federal de Santa MariaCentro de Ciências da SaúdePrograma de Pós-Graduação em Ciências FarmacêuticasUFSMBrasilAnálises Clínicas e ToxicológicasAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessPorfirinasFotoinativaçãoOxigênio singleteMicobacteriosesPorphyrinsPhotoinactivationSinglet oxygenMycobacteriosisCNPQ::CIENCIAS DA SAUDE::FARMACIAFotoinativação de micobactérias de crescimento rápido por porfirinas tetra-catiônicasPhotoinactivation of rapidly growing mycobacteria by tetracationic porphyrinsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisCampos, Marli Matiko Anraku dehttp://lattes.cnpq.br/6421182991125434Iglesias, Bernardo AlmeidaPortela, Ricardo Wagner DiasBotton, Sônia de AvilaLustri, Wilton RogérioAlves, Sydney Hartzhttp://lattes.cnpq.br/8506620006902495Rossi, Grazielle Guidolin400300000005600600600600600600600600ac8e430f-6a47-4d8e-91cd-2fd828e1aa375ed4f0fe-7226-4055-987e-9180c30ade47fc9cad38-6b85-4a25-9108-19542c1775be45e216cb-4bf9-4f5d-ae3d-eea75dce4b39860bd8db-e3f1-4b8e-bb3e-f1c8f0b143068b9c4cbc-9545-47db-bddf-6f1951b5e40284b161a9-565b-45c2-9b62-dfd4be4b3f15reponame:Repositório Institucional Manancial UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMCC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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dc.title.por.fl_str_mv |
Fotoinativação de micobactérias de crescimento rápido por porfirinas tetra-catiônicas |
dc.title.alternative.eng.fl_str_mv |
Photoinactivation of rapidly growing mycobacteria by tetracationic porphyrins |
title |
Fotoinativação de micobactérias de crescimento rápido por porfirinas tetra-catiônicas |
spellingShingle |
Fotoinativação de micobactérias de crescimento rápido por porfirinas tetra-catiônicas Rossi, Grazielle Guidolin Porfirinas Fotoinativação Oxigênio singlete Micobacterioses Porphyrins Photoinactivation Singlet oxygen Mycobacteriosis CNPQ::CIENCIAS DA SAUDE::FARMACIA |
title_short |
Fotoinativação de micobactérias de crescimento rápido por porfirinas tetra-catiônicas |
title_full |
Fotoinativação de micobactérias de crescimento rápido por porfirinas tetra-catiônicas |
title_fullStr |
Fotoinativação de micobactérias de crescimento rápido por porfirinas tetra-catiônicas |
title_full_unstemmed |
Fotoinativação de micobactérias de crescimento rápido por porfirinas tetra-catiônicas |
title_sort |
Fotoinativação de micobactérias de crescimento rápido por porfirinas tetra-catiônicas |
author |
Rossi, Grazielle Guidolin |
author_facet |
Rossi, Grazielle Guidolin |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Campos, Marli Matiko Anraku de |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/6421182991125434 |
dc.contributor.advisor-co1.fl_str_mv |
Iglesias, Bernardo Almeida |
dc.contributor.referee1.fl_str_mv |
Portela, Ricardo Wagner Dias |
dc.contributor.referee2.fl_str_mv |
Botton, Sônia de Avila |
dc.contributor.referee3.fl_str_mv |
Lustri, Wilton Rogério |
dc.contributor.referee4.fl_str_mv |
Alves, Sydney Hartz |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/8506620006902495 |
dc.contributor.author.fl_str_mv |
Rossi, Grazielle Guidolin |
contributor_str_mv |
Campos, Marli Matiko Anraku de Iglesias, Bernardo Almeida Portela, Ricardo Wagner Dias Botton, Sônia de Avila Lustri, Wilton Rogério Alves, Sydney Hartz |
dc.subject.por.fl_str_mv |
Porfirinas Fotoinativação Oxigênio singlete Micobacterioses |
topic |
Porfirinas Fotoinativação Oxigênio singlete Micobacterioses Porphyrins Photoinactivation Singlet oxygen Mycobacteriosis CNPQ::CIENCIAS DA SAUDE::FARMACIA |
dc.subject.eng.fl_str_mv |
Porphyrins Photoinactivation Singlet oxygen Mycobacteriosis |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS DA SAUDE::FARMACIA |
description |
Antimicrobial Photodynamic Inactivation (aPDI) is an emerging non-invasive treatment that involves the use of a photosensitizer (PS), light and molecular oxygen to inactivate microorganisms. Thus, the application of aPDI has been gaining prominence in the field of microbiology, especially in the treatment of infections that persist after conventional antibiotic therapy. In this scenario are included mycobacterioses, because they do not have many therapeutic options available and they require a slow treatment, thus being promising targets of aPDI. The objective of this work is to explore the action of neutral (4-TPyP and 3- TPyP) and tetra-cationic porphyrins, with peripheral complexes of platinum(II) (3-PtTPyP/4- PtTPyP) and palladium(II) (3-PdTPyP/4-PdTPyP), on Rapidly Growing Mycobacteria (RGM) strains that cause skin and mucous infections. In this study were used standard strains of Mycobacteroides abscessus subsp. abscessus (ATCC 19977), Mycobacteroides abscessus subsp. massiliense (ATCC 48898), Mycolicibacterium fortuitum (ATCC 6841), and Mycolicibacterium smegmatis (ATCC 700084). For this purpose, the susceptibility of microorganisms in the planktonic form was obtained through conventional microdilution techniques and by the time-kill curve. The determination of possible reactive oxygen species (ROS) produced by the PS was carried out using compounds that scavenge these reactive species. The impact of these porphyrins on the mycobacterial surface can be visualized and analyzed through images obtained by the Atomic Force Microscopy (AFM) technique. The results demonstrated the significant antimicrobial activity of the studied porphyrins, with emphasis on the meta substituted isomer 3-PtTPyP and 3-PdTPyP. Furthermore, singlet oxygen (¹O2) was the main reactive species detected, being attributed to it the predominant activity in photo-oxidative damages. Finally, the bactericidal activity of Pt(II) and Pd(II) porphyrins was proven in two irradiation sessions, and the AFM images demonstrate the aggression of these porphyrins on the bacterial cell wall, also their influence on nanomechanical adhesion and electrostatic properties. Therefore, porphyrins are a useful and promising tool to eradicate RGM directly via remote control of light irradiation. The impact and scientific contribution of this work are based on the discovery of a potential new therapeutic approach against cutaneous mycobacterial infections and, in addition, they stimulate the deepening of methodologies that aim at the insertion of porphyrins as a new antimicrobial agent. |
publishDate |
2023 |
dc.date.accessioned.fl_str_mv |
2023-03-20T20:03:07Z |
dc.date.available.fl_str_mv |
2023-03-20T20:03:07Z |
dc.date.issued.fl_str_mv |
2023-01-23 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
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doctoralThesis |
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dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/28301 |
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http://repositorio.ufsm.br/handle/1/28301 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.cnpq.fl_str_mv |
400300000005 |
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600 600 600 600 600 600 600 600 |
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Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
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 |
Análises Clínicas e Toxicológicas |
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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