Modulação da resistência a drogas por Furocumarinas e Furocromonas em Staphylococcus aureus
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da UFPB |
Texto Completo: | https://repositorio.ufpb.br/jspui/handle/123456789/26746 |
Resumo: | Microbial resistance to antibiotics has become a worldwide crisis problem, requiring the search for inhibitors of resistance mechanisms that can re-establish the usefulness of these compounds. Furocoumarins and furochromones are natural substances with several important biological properties, such as antibacterial, anti-inflammatory, antitumor, and others. In the present work, substances from the class of furocoumarins and furochromones were evaluated as modulators of drug resistance by inhibition of bacterial efflux systems. The BHI broth microdilution technique was used to determine the minimum inhibitory concentration (MIC) of the compounds against Staphylococcus aureus strain SA-1199B overexpressing the NorA efflux protein. The compounds Ciprofloxacin, Norfloxacin, Ethidium bromide (EtBr), and Berberine were used as NorA substrates to evaluate the modulating action of the substances. No furocoumarin and furochromone tested showed relevant antibacterial activity (MIC ≥512 μg/mL) against S. aureus SA-1199B. However, all showed drug resistance modulating activity. In the modulation assay, the furocoumarins and furochromones were incorporated into the culture medium at subinhibitory concentration (¼ of the MIC). The furocoumarin Isosaxalin showed the best result, modulating 8-fold the minimum inhibitory concentration (MIC) of Norfloxacin, Heraclenol modulated 4-fold and the other furocoumarins (Psoralen, Angelicin, and 3-Carbethoxypsoralen) modulated 2-fold, both, for Norfloxacin and Ciprofloxacin. The furochromones Khellin and Visnagin modulated 2-fold the MIC of Norfloxacin and Ciprofloxacin. The modulation result was similar to EtBr and Berberine indicating that these substances are possible efflux pump inhibitors (EPIs). To understand the differences in their abilities to act as EPIs, a molecular docking study of the furocoumarins and furochromones against the NorA pump model was conducted. Through molecular docking it was possible to theoretically verify the interaction of these substances with the NorA pump, corroborating the microbiological study. |
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Modulação da resistência a drogas por Furocumarinas e Furocromonas em Staphylococcus aureusResistência antibióticaInibidores de bombas de efluxoNorADocagem molecularAntibiotic resistanceEfflux pump inhibitorsMolecular dockingCNPQ::CIENCIAS BIOLOGICAS::BIOLOGIA GERALMicrobial resistance to antibiotics has become a worldwide crisis problem, requiring the search for inhibitors of resistance mechanisms that can re-establish the usefulness of these compounds. Furocoumarins and furochromones are natural substances with several important biological properties, such as antibacterial, anti-inflammatory, antitumor, and others. In the present work, substances from the class of furocoumarins and furochromones were evaluated as modulators of drug resistance by inhibition of bacterial efflux systems. The BHI broth microdilution technique was used to determine the minimum inhibitory concentration (MIC) of the compounds against Staphylococcus aureus strain SA-1199B overexpressing the NorA efflux protein. The compounds Ciprofloxacin, Norfloxacin, Ethidium bromide (EtBr), and Berberine were used as NorA substrates to evaluate the modulating action of the substances. No furocoumarin and furochromone tested showed relevant antibacterial activity (MIC ≥512 μg/mL) against S. aureus SA-1199B. However, all showed drug resistance modulating activity. In the modulation assay, the furocoumarins and furochromones were incorporated into the culture medium at subinhibitory concentration (¼ of the MIC). The furocoumarin Isosaxalin showed the best result, modulating 8-fold the minimum inhibitory concentration (MIC) of Norfloxacin, Heraclenol modulated 4-fold and the other furocoumarins (Psoralen, Angelicin, and 3-Carbethoxypsoralen) modulated 2-fold, both, for Norfloxacin and Ciprofloxacin. The furochromones Khellin and Visnagin modulated 2-fold the MIC of Norfloxacin and Ciprofloxacin. The modulation result was similar to EtBr and Berberine indicating that these substances are possible efflux pump inhibitors (EPIs). To understand the differences in their abilities to act as EPIs, a molecular docking study of the furocoumarins and furochromones against the NorA pump model was conducted. Through molecular docking it was possible to theoretically verify the interaction of these substances with the NorA pump, corroborating the microbiological study.NenhumaA resistência microbiana aos antibióticos se tornou um problema de crise mundial, sendo necessária a busca por inibidores dos mecanismos de resistência que possam reestabelecer a utilidade desses compostos. As furocumarinas e furocromonas são substâncias naturais com diversas propriedades biológicas importantes, tais como, antibacteriana, anti-inflamatória, antitumoral, entre outras. No presente trabalho, foram avaliadas substâncias da classe das furocumarinas e furocromonas como moduladoras da resistência a drogas por inibição de sistemas de efluxo bacteriano. A técnica da microdiluição em caldo BHI foi utilizada para determinar a concentração inibitória mínima (CIM) dos compostos contra a linhagem Staphylococcus aureus SA-1199B que superexpressa a proteína de efluxo NorA. Os compostos Ciprofloxacino, Norfloxacino, Brometo de etídio (EtBr) e Berberina foram utilizados como substratos da NorA para avaliar a ação moduladora das substâncias. Nenhuma furocumarina e furocromona testada apresentou atividade antibacteriana relevante (CIM ≥512 μg/mL) contra S. aureus SA-1199B. Contudo, todas demonstraram atividade de modulação da resistência a drogas. No ensaio de modulação as furocumarinas e furocromonas foram incorporadas ao meio de cultura na concentração subinibitória (¼ da CIM). A furocumarina Isosaxalina apresentou o melhor resultado, reduzindo 8 vezes a CIM de Norfloxacino, o Heraclenol reduziu 4 vezes e as demais furocumarinas (Psoraleno, Angelicina e 3-Carbetoxipsoraleno) reduziram 2 vezes, ambos, a CIM de Norfloxacino e Ciprofloxacino. As furocromonas Quelina e Visnagina reduziram 2 vezes a CIM de Norfloxacino e Ciprofloxacino. O resultado de modulação foi semelhante com o EtBr e com a Berberina, indicando que essas substâncias são possíveis inibidoras de bombas de efluxo (EPIs). A fim de compreender as diferenças nas capacidades de atuar como EPIs, foi conduzido um estudo de docagem molecular das furocumarinas e furocromonas contra o modelo da bomba NorA. Por meio da docagem molecular foi possível verificar teoricamente a interação dessas substâncias com a bomba NorA, corroborando com o estudo microbiológico.Universidade Federal da ParaíbaBrasilBiologia Celular e MolecularPrograma de Pós-Graduação em Biologia Celular e MolecularUFPBSiqueira Júnior, José Pinto dehttp://lattes.cnpq.br/1016153148024105Gurgel, Ana Pavla Almeida Dinizhttp://lattes.cnpq.br/1857108893545275Rodrigues, Damara Freitas2023-04-18T14:54:05Z2022-12-132023-04-18T14:54:05Z2022-10-07info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesishttps://repositorio.ufpb.br/jspui/handle/123456789/26746porAttribution-NoDerivs 3.0 Brazilhttp://creativecommons.org/licenses/by-nd/3.0/br/info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UFPBinstname:Universidade Federal da Paraíba (UFPB)instacron:UFPB2023-04-19T06:04:03Zoai:repositorio.ufpb.br:123456789/26746Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufpb.br/PUBhttp://tede.biblioteca.ufpb.br:8080/oai/requestdiretoria@ufpb.br|| diretoria@ufpb.bropendoar:2023-04-19T06:04:03Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB)false |
dc.title.none.fl_str_mv |
Modulação da resistência a drogas por Furocumarinas e Furocromonas em Staphylococcus aureus |
title |
Modulação da resistência a drogas por Furocumarinas e Furocromonas em Staphylococcus aureus |
spellingShingle |
Modulação da resistência a drogas por Furocumarinas e Furocromonas em Staphylococcus aureus Rodrigues, Damara Freitas Resistência antibiótica Inibidores de bombas de efluxo NorA Docagem molecular Antibiotic resistance Efflux pump inhibitors Molecular docking CNPQ::CIENCIAS BIOLOGICAS::BIOLOGIA GERAL |
title_short |
Modulação da resistência a drogas por Furocumarinas e Furocromonas em Staphylococcus aureus |
title_full |
Modulação da resistência a drogas por Furocumarinas e Furocromonas em Staphylococcus aureus |
title_fullStr |
Modulação da resistência a drogas por Furocumarinas e Furocromonas em Staphylococcus aureus |
title_full_unstemmed |
Modulação da resistência a drogas por Furocumarinas e Furocromonas em Staphylococcus aureus |
title_sort |
Modulação da resistência a drogas por Furocumarinas e Furocromonas em Staphylococcus aureus |
author |
Rodrigues, Damara Freitas |
author_facet |
Rodrigues, Damara Freitas |
author_role |
author |
dc.contributor.none.fl_str_mv |
Siqueira Júnior, José Pinto de http://lattes.cnpq.br/1016153148024105 Gurgel, Ana Pavla Almeida Diniz http://lattes.cnpq.br/1857108893545275 |
dc.contributor.author.fl_str_mv |
Rodrigues, Damara Freitas |
dc.subject.por.fl_str_mv |
Resistência antibiótica Inibidores de bombas de efluxo NorA Docagem molecular Antibiotic resistance Efflux pump inhibitors Molecular docking CNPQ::CIENCIAS BIOLOGICAS::BIOLOGIA GERAL |
topic |
Resistência antibiótica Inibidores de bombas de efluxo NorA Docagem molecular Antibiotic resistance Efflux pump inhibitors Molecular docking CNPQ::CIENCIAS BIOLOGICAS::BIOLOGIA GERAL |
description |
Microbial resistance to antibiotics has become a worldwide crisis problem, requiring the search for inhibitors of resistance mechanisms that can re-establish the usefulness of these compounds. Furocoumarins and furochromones are natural substances with several important biological properties, such as antibacterial, anti-inflammatory, antitumor, and others. In the present work, substances from the class of furocoumarins and furochromones were evaluated as modulators of drug resistance by inhibition of bacterial efflux systems. The BHI broth microdilution technique was used to determine the minimum inhibitory concentration (MIC) of the compounds against Staphylococcus aureus strain SA-1199B overexpressing the NorA efflux protein. The compounds Ciprofloxacin, Norfloxacin, Ethidium bromide (EtBr), and Berberine were used as NorA substrates to evaluate the modulating action of the substances. No furocoumarin and furochromone tested showed relevant antibacterial activity (MIC ≥512 μg/mL) against S. aureus SA-1199B. However, all showed drug resistance modulating activity. In the modulation assay, the furocoumarins and furochromones were incorporated into the culture medium at subinhibitory concentration (¼ of the MIC). The furocoumarin Isosaxalin showed the best result, modulating 8-fold the minimum inhibitory concentration (MIC) of Norfloxacin, Heraclenol modulated 4-fold and the other furocoumarins (Psoralen, Angelicin, and 3-Carbethoxypsoralen) modulated 2-fold, both, for Norfloxacin and Ciprofloxacin. The furochromones Khellin and Visnagin modulated 2-fold the MIC of Norfloxacin and Ciprofloxacin. The modulation result was similar to EtBr and Berberine indicating that these substances are possible efflux pump inhibitors (EPIs). To understand the differences in their abilities to act as EPIs, a molecular docking study of the furocoumarins and furochromones against the NorA pump model was conducted. Through molecular docking it was possible to theoretically verify the interaction of these substances with the NorA pump, corroborating the microbiological study. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-12-13 2022-10-07 2023-04-18T14:54:05Z 2023-04-18T14:54:05Z |
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 |
https://repositorio.ufpb.br/jspui/handle/123456789/26746 |
url |
https://repositorio.ufpb.br/jspui/handle/123456789/26746 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
Attribution-NoDerivs 3.0 Brazil http://creativecommons.org/licenses/by-nd/3.0/br/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NoDerivs 3.0 Brazil http://creativecommons.org/licenses/by-nd/3.0/br/ |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal da Paraíba Brasil Biologia Celular e Molecular Programa de Pós-Graduação em Biologia Celular e Molecular UFPB |
publisher.none.fl_str_mv |
Universidade Federal da Paraíba Brasil Biologia Celular e Molecular Programa de Pós-Graduação em Biologia Celular e Molecular UFPB |
dc.source.none.fl_str_mv |
reponame:Biblioteca Digital de Teses e Dissertações da UFPB instname:Universidade Federal da Paraíba (UFPB) instacron:UFPB |
instname_str |
Universidade Federal da Paraíba (UFPB) |
instacron_str |
UFPB |
institution |
UFPB |
reponame_str |
Biblioteca Digital de Teses e Dissertações da UFPB |
collection |
Biblioteca Digital de Teses e Dissertações da UFPB |
repository.name.fl_str_mv |
Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB) |
repository.mail.fl_str_mv |
diretoria@ufpb.br|| diretoria@ufpb.br |
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1801843008796098560 |