Atividade antimicobacteriana, antibiofilme e avaliação da toxicidade in vitro de complexos metálicos do sulfametoxazol

Detalhes bibliográficos
Autor(a) principal: Siqueira, Fallon dos Santos
Data de Publicação: 2018
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Manancial - Repositório Digital da UFSM
Texto Completo: http://repositorio.ufsm.br/handle/1/20533
Resumo: Rapidly growing mycobacteria (RGM) are opportunistic microorganisms, found in the environment, that can cause both local and disseminated infections. RGM can form structured communities that adhere to solid biotic or abiotic surfaces, characterizing one of their most powerful survival mechanisms, biofilms. Biofilms are considered important sources of infections on biomedical surfaces, and most infections involving biofilm formation are associated with medical device implants such as catheters and prostheses. Therefore, there is an urgent need for new antimicrobial compounds that can combat microbial resistance associated with the formation of RGM biofilms. In recent years, the coordination of metals to classic antimicrobials have shown excellent activity against a variety of microorganisms in planktonic form. In this context, this work aimed to evaluate, for the first time, the antibiofilm action of sulfamethoxazole complexed with Au, Cd, Cu, Ni and Hg on Mycobacterium abscessus (ATCC 19977), Mycobacterium fortuitum (ATCC 6841), Mycobacterium massiliense (ATCC 48898) and six clinical isolates of RGM, as well as to evaluate their safe through cytotoxic assays. Different profiles of susceptibility to drugs used in the clinic and to new compounds were determined in our study and in our results it was demonstrated that sulfamethoxazole derivatives complexed with metals showed, in the great majority of cases, activity superior to that of free sulfamethoxazole and other drugs in inhibiting the growth of RGM. The results demonstrate potentiation of the novel compounds in inhibiting the formation and destruction of biofilms of RGM. The antibiofilm activity of gold-complexed sulfamethoxazole, which was able to completely inhibit biofilm formation, is clearly pronounced. In adittion, this compound had the capacity to destroy the biofilm at all concentrations tested. All cytotoxic data are suggestive that the majority of sulfamethoxazole metallic derivatives are antimicrobial alternatives as well as safe molecules which could be used as potential therapeutic agents for bacterial and biofilm elimination.
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spelling Atividade antimicobacteriana, antibiofilme e avaliação da toxicidade in vitro de complexos metálicos do sulfametoxazolAntimicobacterial and antibiofilm activities and evaluation of in vitro toxicity of sulfamethoxazole metallic complexesMicobactériaBiofilmesResistênciaCompostos inorgânicosMycobacteriaBiofilmsResistenceInorganic compoundsCNPQ::CIENCIAS DA SAUDE::FARMACIARapidly growing mycobacteria (RGM) are opportunistic microorganisms, found in the environment, that can cause both local and disseminated infections. RGM can form structured communities that adhere to solid biotic or abiotic surfaces, characterizing one of their most powerful survival mechanisms, biofilms. Biofilms are considered important sources of infections on biomedical surfaces, and most infections involving biofilm formation are associated with medical device implants such as catheters and prostheses. Therefore, there is an urgent need for new antimicrobial compounds that can combat microbial resistance associated with the formation of RGM biofilms. In recent years, the coordination of metals to classic antimicrobials have shown excellent activity against a variety of microorganisms in planktonic form. In this context, this work aimed to evaluate, for the first time, the antibiofilm action of sulfamethoxazole complexed with Au, Cd, Cu, Ni and Hg on Mycobacterium abscessus (ATCC 19977), Mycobacterium fortuitum (ATCC 6841), Mycobacterium massiliense (ATCC 48898) and six clinical isolates of RGM, as well as to evaluate their safe through cytotoxic assays. Different profiles of susceptibility to drugs used in the clinic and to new compounds were determined in our study and in our results it was demonstrated that sulfamethoxazole derivatives complexed with metals showed, in the great majority of cases, activity superior to that of free sulfamethoxazole and other drugs in inhibiting the growth of RGM. The results demonstrate potentiation of the novel compounds in inhibiting the formation and destruction of biofilms of RGM. The antibiofilm activity of gold-complexed sulfamethoxazole, which was able to completely inhibit biofilm formation, is clearly pronounced. In adittion, this compound had the capacity to destroy the biofilm at all concentrations tested. All cytotoxic data are suggestive that the majority of sulfamethoxazole metallic derivatives are antimicrobial alternatives as well as safe molecules which could be used as potential therapeutic agents for bacterial and biofilm elimination.Micobactérias de crescimento rápido (MCR) são microrganismos oportunistas, encontrados no ambiente, que podem causar infecções locais e disseminadas. As MCR podem formar comunidades estruturadas, que aderem a superfícies bióticas ou abióticas sólidas, caracterizando um de seus mais poderosos mecanismos de sobrevivência, os biofilmes. Os biofilmes são considerados fontes importantes de infecções em superfícies biomédicas e a maioria das infecções envolvendo formação de biofilmes estão associadas a implantes de dispositivos médicos, como cateteres e próteses. Portanto, existe uma necessidade urgente de novos compostos antimicrobianos que possam combater a resistência microbiana associada à formação de biofilmes de MCR. Nos últimos anos, a coordenação de metais a antimicrobianos clássicos vem demonstrando excelente atividade contra uma variedade de microrganismos na forma planctônica. Sendo assim, este trabalho teve como objetivo avaliar, pela primeira vez, a atividade antibiofilme do sulfametoxazol complexado com Au, Cd, Cu, Ni e Hg frente a Mycobacterium abscessus (ATCC 19977), Mycobacterium fortuitum (ATCC 6841), Mycobacterium massiliense (ATCC 48898) e seis isolados clínicos de MCR, bem como avaliar a segurança desses novos compostos através de ensaios citotóxicos. Diferentes perfis de suscetibilidade a fármacos utilizados na clínica e a novos compostos foram determinados em nosso estudo e os resultados demonstraram que os derivados do sulfametoxazol complexados com metais apresentaram, na grande maioria dos casos, atividade superior à do sulfametoxazol livre e outras drogas na inibição do crescimento de MCR. Todos os resultados demonstram a potencialização da atividade dos novos compostos na inibição da formação e destruição de biofilmes de MCR. Destacou-se a atividade antibiofilme do sulfametoxazol complexado com ouro, que foi capaz de inibir completamente a formação de biofilme. Além disso, este composto teve a capacidade de destruir o biofilme em todas as concentrações testadas. Todos os dados citotóxicos são sugestivos de que a maioria dos derivados metálicos do sulfametoxazol são alternativas antimicrobianas, bem como moléculas seguras que podem ser utilizadas como possíveis agentes terapêuticos para a eliminação de bactérias e biofilmes.Universidade Federal de Santa MariaBrasilAnálises Clínicas e ToxicológicasUFSMPrograma de Pós-Graduação em Ciências FarmacêuticasCentro de Ciências da SaúdeCampos, Marli Matiko Anraku dehttp://lattes.cnpq.br/6421182991125434Machado, Alencar KolinskiBrucker, NatáliaSiqueira, Fallon dos Santos2021-04-12T17:06:55Z2021-04-12T17:06:55Z2018-03-05info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://repositorio.ufsm.br/handle/1/20533porAttribution-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:UFSM2022-10-07T17:45:46Zoai:repositorio.ufsm.br:1/20533Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2022-10-07T17:45:46Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false
dc.title.none.fl_str_mv Atividade antimicobacteriana, antibiofilme e avaliação da toxicidade in vitro de complexos metálicos do sulfametoxazol
Antimicobacterial and antibiofilm activities and evaluation of in vitro toxicity of sulfamethoxazole metallic complexes
title Atividade antimicobacteriana, antibiofilme e avaliação da toxicidade in vitro de complexos metálicos do sulfametoxazol
spellingShingle Atividade antimicobacteriana, antibiofilme e avaliação da toxicidade in vitro de complexos metálicos do sulfametoxazol
Siqueira, Fallon dos Santos
Micobactéria
Biofilmes
Resistência
Compostos inorgânicos
Mycobacteria
Biofilms
Resistence
Inorganic compounds
CNPQ::CIENCIAS DA SAUDE::FARMACIA
title_short Atividade antimicobacteriana, antibiofilme e avaliação da toxicidade in vitro de complexos metálicos do sulfametoxazol
title_full Atividade antimicobacteriana, antibiofilme e avaliação da toxicidade in vitro de complexos metálicos do sulfametoxazol
title_fullStr Atividade antimicobacteriana, antibiofilme e avaliação da toxicidade in vitro de complexos metálicos do sulfametoxazol
title_full_unstemmed Atividade antimicobacteriana, antibiofilme e avaliação da toxicidade in vitro de complexos metálicos do sulfametoxazol
title_sort Atividade antimicobacteriana, antibiofilme e avaliação da toxicidade in vitro de complexos metálicos do sulfametoxazol
author Siqueira, Fallon dos Santos
author_facet Siqueira, Fallon dos Santos
author_role author
dc.contributor.none.fl_str_mv Campos, Marli Matiko Anraku de
http://lattes.cnpq.br/6421182991125434
Machado, Alencar Kolinski
Brucker, Natália
dc.contributor.author.fl_str_mv Siqueira, Fallon dos Santos
dc.subject.por.fl_str_mv Micobactéria
Biofilmes
Resistência
Compostos inorgânicos
Mycobacteria
Biofilms
Resistence
Inorganic compounds
CNPQ::CIENCIAS DA SAUDE::FARMACIA
topic Micobactéria
Biofilmes
Resistência
Compostos inorgânicos
Mycobacteria
Biofilms
Resistence
Inorganic compounds
CNPQ::CIENCIAS DA SAUDE::FARMACIA
description Rapidly growing mycobacteria (RGM) are opportunistic microorganisms, found in the environment, that can cause both local and disseminated infections. RGM can form structured communities that adhere to solid biotic or abiotic surfaces, characterizing one of their most powerful survival mechanisms, biofilms. Biofilms are considered important sources of infections on biomedical surfaces, and most infections involving biofilm formation are associated with medical device implants such as catheters and prostheses. Therefore, there is an urgent need for new antimicrobial compounds that can combat microbial resistance associated with the formation of RGM biofilms. In recent years, the coordination of metals to classic antimicrobials have shown excellent activity against a variety of microorganisms in planktonic form. In this context, this work aimed to evaluate, for the first time, the antibiofilm action of sulfamethoxazole complexed with Au, Cd, Cu, Ni and Hg on Mycobacterium abscessus (ATCC 19977), Mycobacterium fortuitum (ATCC 6841), Mycobacterium massiliense (ATCC 48898) and six clinical isolates of RGM, as well as to evaluate their safe through cytotoxic assays. Different profiles of susceptibility to drugs used in the clinic and to new compounds were determined in our study and in our results it was demonstrated that sulfamethoxazole derivatives complexed with metals showed, in the great majority of cases, activity superior to that of free sulfamethoxazole and other drugs in inhibiting the growth of RGM. The results demonstrate potentiation of the novel compounds in inhibiting the formation and destruction of biofilms of RGM. The antibiofilm activity of gold-complexed sulfamethoxazole, which was able to completely inhibit biofilm formation, is clearly pronounced. In adittion, this compound had the capacity to destroy the biofilm at all concentrations tested. All cytotoxic data are suggestive that the majority of sulfamethoxazole metallic derivatives are antimicrobial alternatives as well as safe molecules which could be used as potential therapeutic agents for bacterial and biofilm elimination.
publishDate 2018
dc.date.none.fl_str_mv 2018-03-05
2021-04-12T17:06:55Z
2021-04-12T17:06:55Z
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 http://repositorio.ufsm.br/handle/1/20533
url http://repositorio.ufsm.br/handle/1/20533
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
Análises Clínicas e Toxicológicas
UFSM
Programa de Pós-Graduação em Ciências Farmacêuticas
Centro de Ciências da Saúde
publisher.none.fl_str_mv Universidade Federal de Santa Maria
Brasil
Análises Clínicas e Toxicológicas
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
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