Resistência de biofilmes formados por micobactérias de crescimento rápido frente a antimicrobianos
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Manancial - Repositório Digital da UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/20207 |
Resumo: | Rapidly growing mycobacteria (RGM) are opportunistic pathogens that produce diseases in a variety of clinical settings. The environmental nature of RGM and their ability to assemble biofilms on different surfaces play a key role in their pathogenesis.Biofilms constitute a protected mode of growth that allows microorganisms to survival in hostile environments, being their physiology and behavior significantly different from their planktonic counterparts. Biofilms pose a serious problem for public health because of the increased resistance of biofilm-associated organisms to antimicrobial agents and the potential for these organisms to cause infections. When in biofilms form, mycobacteria are highly resistant to antibacterial treatments. Nanoparticle-based therapies are viable approaches when it comes to treating biofilm associated infections due to chemical and physical properties of such nanostructured systems, granted by a high superficial area to volume ratio. Bearing in mind the importance of comprehending all factors that cause mycobacteriosis treatments to fail, e.g. biofilm formation, the main objective of this study is to evaluate resistance to antimicrobials in RGM biofilms. The tested antimicrobials were amikacin, ciprofloxacin, clarithromycin, doxycycline, imipenem and sulfamethoxazole, which are ordinarily employed in the treatment of mycobacteriosis. For each drug, evaluation was done according to the susceptibility of the pathogen, the ability to inhibit biofilm formation and the resistance of biofilms to antimicrobial activity. Furthermore, due to the broad use of clarithromycin in therapeutic schemes against micobacterial infections, clarithromycin nanocapsules (NC-CLA) were developed and employed. Its antibiofilm properties were evaluated, as were those of the other above stated antimicrobials. Results showed that although the tested antimicrobials are used as an alternative therapy for RGM, Mycobacterium abscessus presented to be resistant to clarithromycin and Mycobacterium massiliense showed a resistant profile to clarithromycin and sulfamethoxazole. Furthermore, the inhibition of biofilm formation and its destruction have not been fully met. The nanoencapsuled clarithromycin form showed higher capability in inhibiting biofilm formation and in microbial pellicle destruction than free clarithromycin, that is, in all tested concentrations and for all three RGM strains that were utilized in the essay. Thus, actions that aim to optimize antimicrobial permeability in the exopolimeric matrix emerge as important prevention strategies against formation of biofilm and in its combat. |
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Resistência de biofilmes formados por micobactérias de crescimento rápido frente a antimicrobianosResistance of biofilms formed by rapidly growing mycobacteria against antimicrobialsMicobactérias de crescimento rápidoBiofilmesResistênciaAntimicrobianosNanocápsulasRapidly growing mycobacteriaBiofilmsResistanceAntimicrobialsNanocapsulesCNPQ::CIENCIAS DA SAUDE::FARMACIARapidly growing mycobacteria (RGM) are opportunistic pathogens that produce diseases in a variety of clinical settings. The environmental nature of RGM and their ability to assemble biofilms on different surfaces play a key role in their pathogenesis.Biofilms constitute a protected mode of growth that allows microorganisms to survival in hostile environments, being their physiology and behavior significantly different from their planktonic counterparts. Biofilms pose a serious problem for public health because of the increased resistance of biofilm-associated organisms to antimicrobial agents and the potential for these organisms to cause infections. When in biofilms form, mycobacteria are highly resistant to antibacterial treatments. Nanoparticle-based therapies are viable approaches when it comes to treating biofilm associated infections due to chemical and physical properties of such nanostructured systems, granted by a high superficial area to volume ratio. Bearing in mind the importance of comprehending all factors that cause mycobacteriosis treatments to fail, e.g. biofilm formation, the main objective of this study is to evaluate resistance to antimicrobials in RGM biofilms. The tested antimicrobials were amikacin, ciprofloxacin, clarithromycin, doxycycline, imipenem and sulfamethoxazole, which are ordinarily employed in the treatment of mycobacteriosis. For each drug, evaluation was done according to the susceptibility of the pathogen, the ability to inhibit biofilm formation and the resistance of biofilms to antimicrobial activity. Furthermore, due to the broad use of clarithromycin in therapeutic schemes against micobacterial infections, clarithromycin nanocapsules (NC-CLA) were developed and employed. Its antibiofilm properties were evaluated, as were those of the other above stated antimicrobials. Results showed that although the tested antimicrobials are used as an alternative therapy for RGM, Mycobacterium abscessus presented to be resistant to clarithromycin and Mycobacterium massiliense showed a resistant profile to clarithromycin and sulfamethoxazole. Furthermore, the inhibition of biofilm formation and its destruction have not been fully met. The nanoencapsuled clarithromycin form showed higher capability in inhibiting biofilm formation and in microbial pellicle destruction than free clarithromycin, that is, in all tested concentrations and for all three RGM strains that were utilized in the essay. Thus, actions that aim to optimize antimicrobial permeability in the exopolimeric matrix emerge as important prevention strategies against formation of biofilm and in its combat.As micobactérias de crescimento rápido (MCR) são agentes patogênicos oportunistas que causam doenças em uma variedade de configurações clínicas. A natureza ambiental das MCR e sua capacidade de desenvolver biofilmes em diferentes superfícies desempenham um papel fundamental na sua patogênese. Os biofilmes constituem um modo protegido de crescimento que permite que os microrganismos sobrevivam em ambientes hostis, sendo sua fisiologia e comportamento significativamente diferentes das suas contrapartes planctônicas. Os biofilmes representam um grave problema para a saúde pública devido ao aumento da resistência aos agentes antimicrobianos e ao potencial desses microrganismos de causarem infecções. Quando em biofilmes, as micobactérias são altamente resistentes aos tratamentos antibacterianos. As terapias baseadas em nanopartículas são abordagens viáveis para tratar infecções associadas a biofilmes devido às suas propriedades químicas e físicas, concedidas pela sua alta relação área superficial / volume.Tendo-se em vista a importância da compreensão de fatores causadores de falência de tratamentos das micobacterioses, como a formação de biofilmes,este trabalho tem como objetivo principal avaliar a resistência a antimicrobianos apresentada por biofilmes de MCR. Foram testados os antimicrobianos amicacina, ciprofloxacino, claritromicina, doxiciclina, imipenem e sulfametoxazol, normalmente empregados no tratamento de micobacterioses. Para cada fármaco, avaliou-se a suscetibilidade do microrganismo, a capacidade de inibição da formação de biofilmes e a resistência dos biofilmes a atuação antimicrobiana. Além disso, devido a claritromicina ser amplamente utilizada em esquemas terapêuticos contra infecções causadas por micobactérias, foram desenvolvidas nanocápsulas de claritromicina (NC-CLA) e suas propriedades antibiofilme avaliadas. Os resultados demostraram que, embora os antimicrobianos testados sejam empregados como alternativa terapêutica para MCR, Mycobacterium abscessus apresentou-se resistente à claritromicina e Mycobacterium massiliense exibiu perfil resistente à claritromicina e ao sulfametoxazol. Além disso, a inibição da formação de biofilmes e a destruição dos mesmos não foram totalmente alcançadas. A claritromicina nanoencapsulada apresentou maior capacidade de inibição da formação do biofilme e destruição da película microbiana do que a claritromicina livre, em todas as concentrações testadas e para as três cepas de MCR utilizadas no ensaio. Dessa forma, ações que otimizam a permeabilidade antimicrobiana na matriz exopolimérica figuram como importantes estratégias de prevenção na formação e combate aos biofilmes.Universidade Federal de Santa MariaBrasilFarmacologiaUFSMPrograma de Pós-Graduação em Ciências FarmacêuticasCentro de Ciências da SaúdeCampos, Marli Matiko Anraku dehttp://lattes.cnpq.br/6421182991125434Rodrigues, Laura Beatrizhttp://lattes.cnpq.br/7750271649441883Silva, Pedro Eduardo Almeida dahttp://lattes.cnpq.br/4577337828511155Botton, Sônia de Avilahttp://lattes.cnpq.br/0814772095155945Alves, Sydney Hartzhttp://lattes.cnpq.br/0330782478769631Flores, Vanessa da Costa2020-12-03T10:57:17Z2020-12-03T10:57:17Z2018-03-28info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfhttp://repositorio.ufsm.br/handle/1/20207porAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSM2020-12-04T06:02:26Zoai:repositorio.ufsm.br:1/20207Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2020-12-04T06:02:26Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.none.fl_str_mv |
Resistência de biofilmes formados por micobactérias de crescimento rápido frente a antimicrobianos Resistance of biofilms formed by rapidly growing mycobacteria against antimicrobials |
title |
Resistência de biofilmes formados por micobactérias de crescimento rápido frente a antimicrobianos |
spellingShingle |
Resistência de biofilmes formados por micobactérias de crescimento rápido frente a antimicrobianos Flores, Vanessa da Costa Micobactérias de crescimento rápido Biofilmes Resistência Antimicrobianos Nanocápsulas Rapidly growing mycobacteria Biofilms Resistance Antimicrobials Nanocapsules CNPQ::CIENCIAS DA SAUDE::FARMACIA |
title_short |
Resistência de biofilmes formados por micobactérias de crescimento rápido frente a antimicrobianos |
title_full |
Resistência de biofilmes formados por micobactérias de crescimento rápido frente a antimicrobianos |
title_fullStr |
Resistência de biofilmes formados por micobactérias de crescimento rápido frente a antimicrobianos |
title_full_unstemmed |
Resistência de biofilmes formados por micobactérias de crescimento rápido frente a antimicrobianos |
title_sort |
Resistência de biofilmes formados por micobactérias de crescimento rápido frente a antimicrobianos |
author |
Flores, Vanessa da Costa |
author_facet |
Flores, Vanessa da Costa |
author_role |
author |
dc.contributor.none.fl_str_mv |
Campos, Marli Matiko Anraku de http://lattes.cnpq.br/6421182991125434 Rodrigues, Laura Beatriz http://lattes.cnpq.br/7750271649441883 Silva, Pedro Eduardo Almeida da http://lattes.cnpq.br/4577337828511155 Botton, Sônia de Avila http://lattes.cnpq.br/0814772095155945 Alves, Sydney Hartz http://lattes.cnpq.br/0330782478769631 |
dc.contributor.author.fl_str_mv |
Flores, Vanessa da Costa |
dc.subject.por.fl_str_mv |
Micobactérias de crescimento rápido Biofilmes Resistência Antimicrobianos Nanocápsulas Rapidly growing mycobacteria Biofilms Resistance Antimicrobials Nanocapsules CNPQ::CIENCIAS DA SAUDE::FARMACIA |
topic |
Micobactérias de crescimento rápido Biofilmes Resistência Antimicrobianos Nanocápsulas Rapidly growing mycobacteria Biofilms Resistance Antimicrobials Nanocapsules CNPQ::CIENCIAS DA SAUDE::FARMACIA |
description |
Rapidly growing mycobacteria (RGM) are opportunistic pathogens that produce diseases in a variety of clinical settings. The environmental nature of RGM and their ability to assemble biofilms on different surfaces play a key role in their pathogenesis.Biofilms constitute a protected mode of growth that allows microorganisms to survival in hostile environments, being their physiology and behavior significantly different from their planktonic counterparts. Biofilms pose a serious problem for public health because of the increased resistance of biofilm-associated organisms to antimicrobial agents and the potential for these organisms to cause infections. When in biofilms form, mycobacteria are highly resistant to antibacterial treatments. Nanoparticle-based therapies are viable approaches when it comes to treating biofilm associated infections due to chemical and physical properties of such nanostructured systems, granted by a high superficial area to volume ratio. Bearing in mind the importance of comprehending all factors that cause mycobacteriosis treatments to fail, e.g. biofilm formation, the main objective of this study is to evaluate resistance to antimicrobials in RGM biofilms. The tested antimicrobials were amikacin, ciprofloxacin, clarithromycin, doxycycline, imipenem and sulfamethoxazole, which are ordinarily employed in the treatment of mycobacteriosis. For each drug, evaluation was done according to the susceptibility of the pathogen, the ability to inhibit biofilm formation and the resistance of biofilms to antimicrobial activity. Furthermore, due to the broad use of clarithromycin in therapeutic schemes against micobacterial infections, clarithromycin nanocapsules (NC-CLA) were developed and employed. Its antibiofilm properties were evaluated, as were those of the other above stated antimicrobials. Results showed that although the tested antimicrobials are used as an alternative therapy for RGM, Mycobacterium abscessus presented to be resistant to clarithromycin and Mycobacterium massiliense showed a resistant profile to clarithromycin and sulfamethoxazole. Furthermore, the inhibition of biofilm formation and its destruction have not been fully met. The nanoencapsuled clarithromycin form showed higher capability in inhibiting biofilm formation and in microbial pellicle destruction than free clarithromycin, that is, in all tested concentrations and for all three RGM strains that were utilized in the essay. Thus, actions that aim to optimize antimicrobial permeability in the exopolimeric matrix emerge as important prevention strategies against formation of biofilm and in its combat. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-03-28 2020-12-03T10:57:17Z 2020-12-03T10:57:17Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/20207 |
url |
http://repositorio.ufsm.br/handle/1/20207 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
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.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Brasil Farmacologia UFSM Programa de Pós-Graduação em Ciências Farmacêuticas Centro de Ciências da Saúde |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Brasil Farmacologia UFSM Programa de Pós-Graduação em Ciências Farmacêuticas Centro de Ciências da Saúde |
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_ |
1805922079167479808 |