Efeito da fluoxetina sobre Burkholderia pseudomallei na forma planctônica e de biofilmes

Detalhes bibliográficos
Ano de defesa: 2023
Autor(a) principal: Araújo, Emanuela Silva de
Orientador(a): Maia, Débora Castelo Branco de Souza Collares
Banca de defesa: Não Informado pela instituição
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Não Informado pela instituição
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
Link de acesso: http://www.repositorio.ufc.br/handle/riufc/72534
Resumo: Melioidosis, caused by Burkholderia pseudomallei bacteria, is a disease of great importance to public health. B. pseudomallei, when in biofilms, tends to be more resistant to antibiotics, resulting in chronic infections. Thus, studies have been conducted in order to identify compounds that interfere with the dynamics of biofilms. Thus, studies have been conducted in order to identify compounds that interfere with the dynamics of biofilms. Thus, this study aimed to evaluate the in vitro effect of fluoxetine hydrochloride (FLU) on the planktonic and biofilm growth of B. pseudomallei and on the antimicrobial susceptibility of these bacteria. The planktonic sensitivity to FLU alone and in combination with antimicrobials was evaluated by the broth microdilution test. The effects of FLU on growing biofilm and on mature biofilms were investigated by evaluating the biomass by crystal violet staining technique and the metabolic activity of the biofilm determined with resazurin. The minimum inhibitory concentration (MIC) of FLU was 19.53 - 312.5 µg/mL. When combined with the antimicrobials, there was a significant increase in the MIC for meropenem (MER), while not changing the MICs of the other drugs. FLU altered the biomass of the growing biofilm at the concentration of MIC/4, while in the mature biofilm there was a reduction (P<0.05) 23 and 30% at concentrations of 625 and 1250 µg/mL, respectively. FLU eradicated the biofilms of B. pseudomallei, showing minimum biofilm eliminating concentration (MBEC) values at concentrations of 1250 - 2500 µg/mL. As for the antimicrobial drugs, no MBEC values were found for AMC and the MBEC ranges for MER were 16 - 256 µg/mL and >256 µg/mL for doxycycline (DOX). When used at MIC concentration (19.53 - 312.5 µg/mL), FLU did not reduce the MBEC values for AMC, MER and DOX against mature biofilms of Burkholderia pseudomallei, but when used at MBEC/4 concentration (312.5 and 625 µg/mL), there was a statistically significant reduction (P<0.05) for all combinations tested on mature biofilms of B. pseudomallei. FLU inhibits planktonic growth of B. pseudomallei, kills growing biofilms and mature biofilms, and sensitizes them to AMC, MER and DOX drugs.
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spelling Araújo, Emanuela Silva deGuedes, Gláucia Morgana de MeloMaia, Débora Castelo Branco de Souza Collares2023-05-26T17:10:15Z2023-05-26T17:10:15Z2023ARAÚJO, Emanuela Silva de. Efeito da fluoxetina sobre Burkholderia pseudomallei na forma planctônica e de biofilmes. 2023. Dissertação (Mestrado em Microbiologia Médica) – Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2023. Disponível em: http://www.repositorio.ufc.br/handle/riufc/72534. Acesso em: 26 maio 2023.http://www.repositorio.ufc.br/handle/riufc/72534Melioidosis, caused by Burkholderia pseudomallei bacteria, is a disease of great importance to public health. B. pseudomallei, when in biofilms, tends to be more resistant to antibiotics, resulting in chronic infections. Thus, studies have been conducted in order to identify compounds that interfere with the dynamics of biofilms. Thus, studies have been conducted in order to identify compounds that interfere with the dynamics of biofilms. Thus, this study aimed to evaluate the in vitro effect of fluoxetine hydrochloride (FLU) on the planktonic and biofilm growth of B. pseudomallei and on the antimicrobial susceptibility of these bacteria. The planktonic sensitivity to FLU alone and in combination with antimicrobials was evaluated by the broth microdilution test. The effects of FLU on growing biofilm and on mature biofilms were investigated by evaluating the biomass by crystal violet staining technique and the metabolic activity of the biofilm determined with resazurin. The minimum inhibitory concentration (MIC) of FLU was 19.53 - 312.5 µg/mL. When combined with the antimicrobials, there was a significant increase in the MIC for meropenem (MER), while not changing the MICs of the other drugs. FLU altered the biomass of the growing biofilm at the concentration of MIC/4, while in the mature biofilm there was a reduction (P<0.05) 23 and 30% at concentrations of 625 and 1250 µg/mL, respectively. FLU eradicated the biofilms of B. pseudomallei, showing minimum biofilm eliminating concentration (MBEC) values at concentrations of 1250 - 2500 µg/mL. As for the antimicrobial drugs, no MBEC values were found for AMC and the MBEC ranges for MER were 16 - 256 µg/mL and >256 µg/mL for doxycycline (DOX). When used at MIC concentration (19.53 - 312.5 µg/mL), FLU did not reduce the MBEC values for AMC, MER and DOX against mature biofilms of Burkholderia pseudomallei, but when used at MBEC/4 concentration (312.5 and 625 µg/mL), there was a statistically significant reduction (P<0.05) for all combinations tested on mature biofilms of B. pseudomallei. FLU inhibits planktonic growth of B. pseudomallei, kills growing biofilms and mature biofilms, and sensitizes them to AMC, MER and DOX drugs.A melioidose, causada pela bactéria Burkholderia pseudomallei, é uma doença de grande importância para a saúde pública. B. pseudomallei, quando em biofilmes tende a ter uma maior resistência aos antibióticos, resultando na cronicidade das infecções. Com isso, estudos têm sido realizados com o intuito de identificar compostos que interfiram na dinâmica dos biofilmes. Dessa forma, esse estudo se propôs a avaliar o efeito in vitro da droga cloridrato de fluoxetina (FLU) sobre o crescimento planctônico e de biofilme de B. pseudomallei e sobre a sensibilidade antimicrobiana dessa bactéria. A sensibilidade planctônica à FLU, isolada e combinada com os antimicrobianos, foi avaliada pelo teste de microdiluição em caldo. Foram investigados os efeitos da FLU sobre a formação dos biofilmes e sobre biofilmes maduros por meio da avaliação da biomassa pela técnica de coloração por cristal violeta e da atividade metabólica do biofilme determinada com resazurina. A concentração inibitória mínima (CIM) da FLU foi de 19,53 – 312,5 µg/mL. Quando combinada com os antimicrobianos, houve aumento significativo na CIM para meropenem (MER), não alterando as CIMs das outras drogas. A FLU alterou a biomassa do biofilme em formação na concentração de CIM/4, enquanto no biofilme maduro houve uma redução (P<0,05) 23 e 30% nas concentrações de 625 e 1250 µg/mL, respectivamente. A FLU erradicou os biofilmes de B. pseudomallei, apresentando valores de concentrações eliminatórias mínimas do biofilme (CEMB) nas concentrações de 1250 - 2500 µg/mL. Quanto às drogas antimicrobianas, não foram encontrados valores de CEMB para AMC e os intervalos de CEMB para MER foram 16 – 256 µg/mL e > 256 µg/mL para doxiciclina (DOX). Quando utilizada na concentração de CIM (19,53 – 312,5 µg/mL), a FLU não reduziu os valores de CEMB para AMC, MER e DOX contra biofilmes maduros de B. pseudomallei, porém quando utilizada na concentração de CEMB/4 (312,5 e 625 µg/mL), houve redução estatisticamente significativa (P<0,05) para todas as combinações testadas nos biofilmes maduros de B. pseudomallei. A FLU inibe o crescimento planctônico de B. pseudomallei, mata os biofilmes em formação e maduro, além de sensibilizá-los as drogas AMC, MER e DOX.Burkholderia pseudomalleiBiofilmesAnti-InfecciososFluoxetinaEfeito da fluoxetina sobre Burkholderia pseudomallei na forma planctônica e de biofilmesEffect of fluoxetine on Burkholderia pseudomallei in planktonic and biofilm forminfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisporreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFCinfo:eu-repo/semantics/openAccessORIGINAL2023_dis_esaraujo.pdf2023_dis_esaraujo.pdfapplication/pdf1531560http://repositorio.ufc.br/bitstream/riufc/72534/4/2023_dis_esaraujo.pdfa0627a69c41f6c844b437b1f6158fd1cMD54LICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://repositorio.ufc.br/bitstream/riufc/72534/6/license.txt8a4605be74aa9ea9d79846c1fba20a33MD56riufc/725342023-05-26 14:12:18.665oai:repositorio.ufc.br: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Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2023-05-26T17:12:18Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.pt_BR.fl_str_mv Efeito da fluoxetina sobre Burkholderia pseudomallei na forma planctônica e de biofilmes
dc.title.en.pt_BR.fl_str_mv Effect of fluoxetine on Burkholderia pseudomallei in planktonic and biofilm form
title Efeito da fluoxetina sobre Burkholderia pseudomallei na forma planctônica e de biofilmes
spellingShingle Efeito da fluoxetina sobre Burkholderia pseudomallei na forma planctônica e de biofilmes
Araújo, Emanuela Silva de
Burkholderia pseudomallei
Biofilmes
Anti-Infecciosos
Fluoxetina
title_short Efeito da fluoxetina sobre Burkholderia pseudomallei na forma planctônica e de biofilmes
title_full Efeito da fluoxetina sobre Burkholderia pseudomallei na forma planctônica e de biofilmes
title_fullStr Efeito da fluoxetina sobre Burkholderia pseudomallei na forma planctônica e de biofilmes
title_full_unstemmed Efeito da fluoxetina sobre Burkholderia pseudomallei na forma planctônica e de biofilmes
title_sort Efeito da fluoxetina sobre Burkholderia pseudomallei na forma planctônica e de biofilmes
author Araújo, Emanuela Silva de
author_facet Araújo, Emanuela Silva de
author_role author
dc.contributor.co-advisor.none.fl_str_mv Guedes, Gláucia Morgana de Melo
dc.contributor.author.fl_str_mv Araújo, Emanuela Silva de
dc.contributor.advisor1.fl_str_mv Maia, Débora Castelo Branco de Souza Collares
contributor_str_mv Maia, Débora Castelo Branco de Souza Collares
dc.subject.por.fl_str_mv Burkholderia pseudomallei
Biofilmes
Anti-Infecciosos
Fluoxetina
topic Burkholderia pseudomallei
Biofilmes
Anti-Infecciosos
Fluoxetina
description Melioidosis, caused by Burkholderia pseudomallei bacteria, is a disease of great importance to public health. B. pseudomallei, when in biofilms, tends to be more resistant to antibiotics, resulting in chronic infections. Thus, studies have been conducted in order to identify compounds that interfere with the dynamics of biofilms. Thus, studies have been conducted in order to identify compounds that interfere with the dynamics of biofilms. Thus, this study aimed to evaluate the in vitro effect of fluoxetine hydrochloride (FLU) on the planktonic and biofilm growth of B. pseudomallei and on the antimicrobial susceptibility of these bacteria. The planktonic sensitivity to FLU alone and in combination with antimicrobials was evaluated by the broth microdilution test. The effects of FLU on growing biofilm and on mature biofilms were investigated by evaluating the biomass by crystal violet staining technique and the metabolic activity of the biofilm determined with resazurin. The minimum inhibitory concentration (MIC) of FLU was 19.53 - 312.5 µg/mL. When combined with the antimicrobials, there was a significant increase in the MIC for meropenem (MER), while not changing the MICs of the other drugs. FLU altered the biomass of the growing biofilm at the concentration of MIC/4, while in the mature biofilm there was a reduction (P<0.05) 23 and 30% at concentrations of 625 and 1250 µg/mL, respectively. FLU eradicated the biofilms of B. pseudomallei, showing minimum biofilm eliminating concentration (MBEC) values at concentrations of 1250 - 2500 µg/mL. As for the antimicrobial drugs, no MBEC values were found for AMC and the MBEC ranges for MER were 16 - 256 µg/mL and >256 µg/mL for doxycycline (DOX). When used at MIC concentration (19.53 - 312.5 µg/mL), FLU did not reduce the MBEC values for AMC, MER and DOX against mature biofilms of Burkholderia pseudomallei, but when used at MBEC/4 concentration (312.5 and 625 µg/mL), there was a statistically significant reduction (P<0.05) for all combinations tested on mature biofilms of B. pseudomallei. FLU inhibits planktonic growth of B. pseudomallei, kills growing biofilms and mature biofilms, and sensitizes them to AMC, MER and DOX drugs.
publishDate 2023
dc.date.accessioned.fl_str_mv 2023-05-26T17:10:15Z
dc.date.available.fl_str_mv 2023-05-26T17:10:15Z
dc.date.issued.fl_str_mv 2023
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dc.identifier.citation.fl_str_mv ARAÚJO, Emanuela Silva de. Efeito da fluoxetina sobre Burkholderia pseudomallei na forma planctônica e de biofilmes. 2023. Dissertação (Mestrado em Microbiologia Médica) – Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2023. Disponível em: http://www.repositorio.ufc.br/handle/riufc/72534. Acesso em: 26 maio 2023.
dc.identifier.uri.fl_str_mv http://www.repositorio.ufc.br/handle/riufc/72534
identifier_str_mv ARAÚJO, Emanuela Silva de. Efeito da fluoxetina sobre Burkholderia pseudomallei na forma planctônica e de biofilmes. 2023. Dissertação (Mestrado em Microbiologia Médica) – Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2023. Disponível em: http://www.repositorio.ufc.br/handle/riufc/72534. Acesso em: 26 maio 2023.
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