Potencial de virulência de amostras de Corynebacterium spp. isoladas de pacientes hospitalizados

Detalhes bibliográficos
Autor(a) principal: Heggendornn, Lorraine Herdy
Data de Publicação: 2022
Outros Autores: lorraineheggendornn@gmail.com
Tipo de documento: Tese
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da UERJ
Texto Completo: http://www.bdtd.uerj.br/handle/1/20870
Resumo: In the last decades, non-diphtheritic corynebacteria have emerged as true pathogens of nosocomial infections and the pattern of resistance of these microorganisms to multiple drugs has been emphasized. However, the virulence mechanisms of these pathogens are not well understood. In this perspective, the present work aimed to investigate the virulence potential of Corynebacterium spp. isolated from human clinical material and to characterize the genetic determinants involved with a Metallo-Beta-Lactamase (MBL) phenotype in our bacterial strains. In this study, clinical strains of Corynebacteirum amycolatum (3 strains), Corynebacterium accolens (4 strains), Corynebacterium minutissimum (1 strain) and Corynebacterium falsenii (1 strain) were studied. Assays of adherence and invasion to the U-397 macrophage lineage were performed at 3 and 6 hours. The nematode Caenorhabditis elegans was used as an in vivo model for the virulence assay. Corynebacterium spp. phenotypically producing MBL were submitted to the polymerase chain reaction technique to identify the genetic determinant responsible for bacterial resistance. All samples showed adherence to the macrophage lineage U-937. All strains of Corynebacterium spp. caused a decline in the survival curve of C. elegans, when compared to the survival curve of nematodes exposed to the control strain. Regarding the morphology and development of the nematodes infected by Corynebacterium spp., 100.0% of the strains caused deformation of the anal region (Dar phenotype) and abdominal distension. The “worm bagging” phenotype was observed for all strains tested. The bla gene, which encodes a class A beta-lactamase, was detected in multidrug-resistant strains of C. amycolatum. In conclusion, the study highlights the relevance of Corynebacterium spp. as a multidrug-resistant nosocomial pathogen. To the best of our knowledge, this is the first identification of imipenem-resistant C. amycolatum, showing the production of MBL and positive for bla gene. Finally, the bla gene was sequenced and the result deposited in GenBank. Furthermore, the results showed interaction between the nematode and Corynebacterium spp. resulted in morphological changes that may provide insights into aspects of bacterial pathogenicity and mechanisms underlying physiological processes in humans. Thus, it is suggested that medical surveillance programs include control strategies to reduce potential risk factors for nosocomial infections by Corynebacterium spp
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spelling Sant'Anna, Louisy Sanches dos Santoshttp://lattes.cnpq.br/5999066009401057Póvoa, Helvécio Cardoso Corrêahttp://lattes.cnpq.br/3238287761987937Guaraldi, Ana Luíza de Mattoshttp://lattes.cnpq.br/8091118564093203Ribeiro, Paula Marcele Afonso Pereirahttp://lattes.cnpq.br/1160678854192639Longo, Luís Guilherme de AraújoSouza, Cassius dehttp://lattes.cnpq.br/3804846868751208http://lattes.cnpq.br/4871174789249528Heggendornn, Lorraine Herdylorraineheggendornn@gmail.com2024-01-03T18:39:24Z2022-09-28HEGGENDORNN, Lorraine Herdy. Potencial de virulência de amostras de Corynebacterium spp. isoladas de pacientes hospitalizados. 2022. 92 f. Tese (Doutorado em Microbiologia) - Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2022.http://www.bdtd.uerj.br/handle/1/20870In the last decades, non-diphtheritic corynebacteria have emerged as true pathogens of nosocomial infections and the pattern of resistance of these microorganisms to multiple drugs has been emphasized. However, the virulence mechanisms of these pathogens are not well understood. In this perspective, the present work aimed to investigate the virulence potential of Corynebacterium spp. isolated from human clinical material and to characterize the genetic determinants involved with a Metallo-Beta-Lactamase (MBL) phenotype in our bacterial strains. In this study, clinical strains of Corynebacteirum amycolatum (3 strains), Corynebacterium accolens (4 strains), Corynebacterium minutissimum (1 strain) and Corynebacterium falsenii (1 strain) were studied. Assays of adherence and invasion to the U-397 macrophage lineage were performed at 3 and 6 hours. The nematode Caenorhabditis elegans was used as an in vivo model for the virulence assay. Corynebacterium spp. phenotypically producing MBL were submitted to the polymerase chain reaction technique to identify the genetic determinant responsible for bacterial resistance. All samples showed adherence to the macrophage lineage U-937. All strains of Corynebacterium spp. caused a decline in the survival curve of C. elegans, when compared to the survival curve of nematodes exposed to the control strain. Regarding the morphology and development of the nematodes infected by Corynebacterium spp., 100.0% of the strains caused deformation of the anal region (Dar phenotype) and abdominal distension. The “worm bagging” phenotype was observed for all strains tested. The bla gene, which encodes a class A beta-lactamase, was detected in multidrug-resistant strains of C. amycolatum. In conclusion, the study highlights the relevance of Corynebacterium spp. as a multidrug-resistant nosocomial pathogen. To the best of our knowledge, this is the first identification of imipenem-resistant C. amycolatum, showing the production of MBL and positive for bla gene. Finally, the bla gene was sequenced and the result deposited in GenBank. Furthermore, the results showed interaction between the nematode and Corynebacterium spp. resulted in morphological changes that may provide insights into aspects of bacterial pathogenicity and mechanisms underlying physiological processes in humans. Thus, it is suggested that medical surveillance programs include control strategies to reduce potential risk factors for nosocomial infections by Corynebacterium sppNas últimas décadas, as corinebactérias não-diftéricas emergiram como verdadeiros patógenos de infecções nosocomiais e o padrão de resistência destes microrganismos a múltiplas drogas têm sido enfatizado. Entretanto, os mecanismos de virulência destes patógenos não se encontram bem elucidados. Nesta perspectiva, o presente trabalho teve como objetivo investigar o potencial de virulência de cepas de Corynebacterium spp. isoladas de material clínico humano e caracterizar os determinantes genéticos envolvidos com fenótipo de Metalo-Beta-Lactamase (MBL) positivo nas amostras bacterianas estudadas. Neste estudo, foram utilizadas amostras clínicas das espécies Corynebacterium amycolatum (3 cepas), Corynebacterium accolens (4 cepas), Corynebacterium minutissimum (1 cepa) e Corynebacterium falsenii (1 cepa). Os ensaios de invasão foram realizados com macrófagos U-937 no intervalo de 3 e 6 horas. O nematódeo Caenorhabditis elegans foi empregado como modelo in vivo para o ensaio de virulência. Amostras de Corynebacterium spp. fenotipicamente produtoras de MBL foram submetidas a técnica da reação em cadeia da polimerase, para a identificação do determinante genético responsável pela resistência bacteriana. Todas as amostras foram capazes de aderir aos macrófagos U-937. Todas as cepas de Corynebacterium spp. causaram declínio da curva de sobrevivência de C. elegans, quando comparadas à curva de sobrevivência dos nematódeos expostos à cepa controle. Quanto à morfologia e ao desenvolvimento dos nematódeos infectados por Corynebacterium spp., 100,0% das cepas apresentaram deformação da região anal (fenótipo Dar) e distensão abdominal em C. elegans. O fenótipo “Worm bagging” foi observado em todas as amostras testadas. O gene bla, que codifica uma beta-lactamase classe A, foi detectado em cepas de C. amycolatum multirresistentes. Por fim, as amostras bla gene positivas foram encaminhadas para sequenciamento e o resultado depositado no GenBank. Em conclusão, o estudo destaca a relevância de Corynebacterium spp. como um patógeno nosocomial multirresistente. De acordo com o conhecimento atual, esta é a primeira identificação de C. amycolatum resistente ao imipenem, evidenciando a produção de MBL e gene bla positivo. Além disso, os resultados mostraram que a interação entre o nematódeo e Corynebacterium spp. resultou em alterações morfológicas que podem fornecer conhecimentos sobre aspectos da patogenicidade bacteriana e mecanismos subjacentes aos processos fisiológicos em humanos. Dessa forma, sugere-se que os programas de vigilância médica incluam estratégias de controle para diminuir os potenciais fatores de risco de infecções nosocomiais por Corynebacterium sppSubmitted by Felipe CB/A (felipebibliotecario@gmail.com) on 2024-01-03T18:39:24Z No. of bitstreams: 1 Tese - Lorraine Herdy Heggendornn - 2022 - Completa.pdf: 920623 bytes, checksum: 20f3a485213889f0d7dc2554ca8066ca (MD5)Made available in DSpace on 2024-01-03T18:39:24Z (GMT). No. of bitstreams: 1 Tese - Lorraine Herdy Heggendornn - 2022 - Completa.pdf: 920623 bytes, checksum: 20f3a485213889f0d7dc2554ca8066ca (MD5) Previous issue date: 2022-09-28Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESapplication/pdfporUniversidade do Estado do Rio de JaneiroPrograma de Pós-Graduação em MicrobiologiaUERJBrasilCentro Biomédico::Faculdade de Ciências MédicasVirulence potentialCellular interactionMetallo-beta-lactamaseCorynebacterium spp. – PatogenicidadeCaenorhabditis elegansResistência Microbiana a Medicamentos – GenéticaInfecção hospitalarVirulênciaMacrófagos U-937Metalo-Beta-LactamaseCIENCIAS BIOLOGICAS::MICROBIOLOGIAPotencial de virulência de amostras de Corynebacterium spp. isoladas de pacientes hospitalizadosVirulence potential of Corynebacterium spp. isolated from hospitalized patientsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UERJinstname:Universidade do Estado do Rio de Janeiro (UERJ)instacron:UERJORIGINALTese - Lorraine Herdy Heggendornn - 2022 - Completa.pdfTese - Lorraine Herdy Heggendornn - 2022 - Completa.pdfapplication/pdf920623http://www.bdtd.uerj.br/bitstream/1/20870/2/Tese+-+Lorraine+Herdy+Heggendornn+-+2022+-+Completa.pdf20f3a485213889f0d7dc2554ca8066caMD52LICENSElicense.txtlicense.txttext/plain; charset=utf-82123http://www.bdtd.uerj.br/bitstream/1/20870/1/license.txte5502652da718045d7fcd832b79fca29MD511/208702024-02-26 19:54:38.835oai:www.bdtd.uerj.br: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Biblioteca Digital de Teses e Dissertaçõeshttp://www.bdtd.uerj.br/PUBhttps://www.bdtd.uerj.br:8443/oai/requestbdtd.suporte@uerj.bropendoar:29032024-02-26T22:54:38Biblioteca Digital de Teses e Dissertações da UERJ - Universidade do Estado do Rio de Janeiro (UERJ)false
dc.title.por.fl_str_mv Potencial de virulência de amostras de Corynebacterium spp. isoladas de pacientes hospitalizados
dc.title.alternative.eng.fl_str_mv Virulence potential of Corynebacterium spp. isolated from hospitalized patients
title Potencial de virulência de amostras de Corynebacterium spp. isoladas de pacientes hospitalizados
spellingShingle Potencial de virulência de amostras de Corynebacterium spp. isoladas de pacientes hospitalizados
Heggendornn, Lorraine Herdy
Virulence potential
Cellular interaction
Metallo-beta-lactamase
Corynebacterium spp. – Patogenicidade
Caenorhabditis elegans
Resistência Microbiana a Medicamentos – Genética
Infecção hospitalar
Virulência
Macrófagos U-937
Metalo-Beta-Lactamase
CIENCIAS BIOLOGICAS::MICROBIOLOGIA
title_short Potencial de virulência de amostras de Corynebacterium spp. isoladas de pacientes hospitalizados
title_full Potencial de virulência de amostras de Corynebacterium spp. isoladas de pacientes hospitalizados
title_fullStr Potencial de virulência de amostras de Corynebacterium spp. isoladas de pacientes hospitalizados
title_full_unstemmed Potencial de virulência de amostras de Corynebacterium spp. isoladas de pacientes hospitalizados
title_sort Potencial de virulência de amostras de Corynebacterium spp. isoladas de pacientes hospitalizados
author Heggendornn, Lorraine Herdy
author_facet Heggendornn, Lorraine Herdy
lorraineheggendornn@gmail.com
author_role author
author2 lorraineheggendornn@gmail.com
author2_role author
dc.contributor.advisor1.fl_str_mv Sant'Anna, Louisy Sanches dos Santos
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/5999066009401057
dc.contributor.advisor-co1.fl_str_mv Póvoa, Helvécio Cardoso Corrêa
dc.contributor.advisor-co1Lattes.fl_str_mv http://lattes.cnpq.br/3238287761987937
dc.contributor.referee1.fl_str_mv Guaraldi, Ana Luíza de Mattos
dc.contributor.referee1Lattes.fl_str_mv http://lattes.cnpq.br/8091118564093203
dc.contributor.referee2.fl_str_mv Ribeiro, Paula Marcele Afonso Pereira
dc.contributor.referee2Lattes.fl_str_mv http://lattes.cnpq.br/1160678854192639
dc.contributor.referee3.fl_str_mv Longo, Luís Guilherme de Araújo
dc.contributor.referee4.fl_str_mv Souza, Cassius de
dc.contributor.referee4Lattes.fl_str_mv http://lattes.cnpq.br/3804846868751208
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/4871174789249528
dc.contributor.author.fl_str_mv Heggendornn, Lorraine Herdy
lorraineheggendornn@gmail.com
contributor_str_mv Sant'Anna, Louisy Sanches dos Santos
Póvoa, Helvécio Cardoso Corrêa
Guaraldi, Ana Luíza de Mattos
Ribeiro, Paula Marcele Afonso Pereira
Longo, Luís Guilherme de Araújo
Souza, Cassius de
dc.subject.eng.fl_str_mv Virulence potential
Cellular interaction
Metallo-beta-lactamase
topic Virulence potential
Cellular interaction
Metallo-beta-lactamase
Corynebacterium spp. – Patogenicidade
Caenorhabditis elegans
Resistência Microbiana a Medicamentos – Genética
Infecção hospitalar
Virulência
Macrófagos U-937
Metalo-Beta-Lactamase
CIENCIAS BIOLOGICAS::MICROBIOLOGIA
dc.subject.por.fl_str_mv Corynebacterium spp. – Patogenicidade
Caenorhabditis elegans
Resistência Microbiana a Medicamentos – Genética
Infecção hospitalar
Virulência
Macrófagos U-937
Metalo-Beta-Lactamase
dc.subject.cnpq.fl_str_mv CIENCIAS BIOLOGICAS::MICROBIOLOGIA
description In the last decades, non-diphtheritic corynebacteria have emerged as true pathogens of nosocomial infections and the pattern of resistance of these microorganisms to multiple drugs has been emphasized. However, the virulence mechanisms of these pathogens are not well understood. In this perspective, the present work aimed to investigate the virulence potential of Corynebacterium spp. isolated from human clinical material and to characterize the genetic determinants involved with a Metallo-Beta-Lactamase (MBL) phenotype in our bacterial strains. In this study, clinical strains of Corynebacteirum amycolatum (3 strains), Corynebacterium accolens (4 strains), Corynebacterium minutissimum (1 strain) and Corynebacterium falsenii (1 strain) were studied. Assays of adherence and invasion to the U-397 macrophage lineage were performed at 3 and 6 hours. The nematode Caenorhabditis elegans was used as an in vivo model for the virulence assay. Corynebacterium spp. phenotypically producing MBL were submitted to the polymerase chain reaction technique to identify the genetic determinant responsible for bacterial resistance. All samples showed adherence to the macrophage lineage U-937. All strains of Corynebacterium spp. caused a decline in the survival curve of C. elegans, when compared to the survival curve of nematodes exposed to the control strain. Regarding the morphology and development of the nematodes infected by Corynebacterium spp., 100.0% of the strains caused deformation of the anal region (Dar phenotype) and abdominal distension. The “worm bagging” phenotype was observed for all strains tested. The bla gene, which encodes a class A beta-lactamase, was detected in multidrug-resistant strains of C. amycolatum. In conclusion, the study highlights the relevance of Corynebacterium spp. as a multidrug-resistant nosocomial pathogen. To the best of our knowledge, this is the first identification of imipenem-resistant C. amycolatum, showing the production of MBL and positive for bla gene. Finally, the bla gene was sequenced and the result deposited in GenBank. Furthermore, the results showed interaction between the nematode and Corynebacterium spp. resulted in morphological changes that may provide insights into aspects of bacterial pathogenicity and mechanisms underlying physiological processes in humans. Thus, it is suggested that medical surveillance programs include control strategies to reduce potential risk factors for nosocomial infections by Corynebacterium spp
publishDate 2022
dc.date.issued.fl_str_mv 2022-09-28
dc.date.accessioned.fl_str_mv 2024-01-03T18:39:24Z
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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dc.identifier.citation.fl_str_mv HEGGENDORNN, Lorraine Herdy. Potencial de virulência de amostras de Corynebacterium spp. isoladas de pacientes hospitalizados. 2022. 92 f. Tese (Doutorado em Microbiologia) - Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2022.
dc.identifier.uri.fl_str_mv http://www.bdtd.uerj.br/handle/1/20870
identifier_str_mv HEGGENDORNN, Lorraine Herdy. Potencial de virulência de amostras de Corynebacterium spp. isoladas de pacientes hospitalizados. 2022. 92 f. Tese (Doutorado em Microbiologia) - Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2022.
url http://www.bdtd.uerj.br/handle/1/20870
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dc.publisher.none.fl_str_mv Universidade do Estado do Rio de Janeiro
dc.publisher.program.fl_str_mv Programa de Pós-Graduação em Microbiologia
dc.publisher.initials.fl_str_mv UERJ
dc.publisher.country.fl_str_mv Brasil
dc.publisher.department.fl_str_mv Centro Biomédico::Faculdade de Ciências Médicas
publisher.none.fl_str_mv Universidade do Estado do Rio de Janeiro
dc.source.none.fl_str_mv reponame:Biblioteca Digital de Teses e Dissertações da UERJ
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