Avaliação da influência de OxyR na resposta ao estresse e na virulência de Corynebacterium diphtheriae
Ano de defesa: | 2018 |
---|---|
Autor(a) principal: | |
Outros Autores: | |
Orientador(a): | |
Banca de defesa: | , , , |
Tipo de documento: | Tese |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade do Estado do Rio de Janeiro
|
Programa de Pós-Graduação: |
Programa de Pós-Graduação em Microbiologia
|
Departamento: |
Centro Biomédico::Faculdade de Ciências Médicas
|
País: |
Brasil
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://www.bdtd.uerj.br/handle/1/20207 |
Resumo: | Corynebacterium diphtheriae, the major etiological agent of diphtheria, has been associated to invasive infections, regardless of diphtheria toxin production. This fact suggests that others virulence factors, besides to the diphtheria toxin production, are involved in the pathogenicity of this microorganism. Several mechanisms of survival and dissemination of the microorganism, both in the host and in the environment, contribute to the bacterial infections pathogenesis. Amongst the pathogenic mechanisms, the response of C. diphtheriae to different stress responses still remain misunderstood. The aim of this study was to investigate the role of the OxyR, already described as an important regulator involved in the resistance and virulence of other bacterial species, in the C. diphtheriae pathogenesis. Therefore, the parental strains CDC-E8392 and the mutant (LDCIC-L2), unable to produce OxyR, were compared for gene expression and survival ability under stress conditions. In addition, both strains were compared for their pathogenic potential, through interaction with epithelial cells and macrophages, biofilm formation, interaction with plasma and extracellular matrix proteins assays and in vivo infection to C. elegans nematodes and in Swiss Webster mice. The results indicated that OxyR regulates negatively the catalase expression and response to H2O2. The interruption of expression of OxyR also modulated the expression of cspA and the resistance to oxidative stress generated by ozone. The mutant strain showed a significant reduction in the capacity of binding to fibronectin, collagen and fibrinogen. The influence of OxyR on the virulence properties of C. diphtheriae was also evidenced by ability of the mutant strain to survive in the intracytoplasmic compartment of human epithelial cells and macrophage and to induce a more evident inflammatory process in knee joint in mice. In addition, despite the cellular infection of respiratory cells by C. diphtheriae strains lead to increased production of ROS and RNS, the OxyR– mutant strain induced a significantly higher production of NO than the cells infected with the wild type strain. However, interruption of OxyR did not induce a significant difference in both biofilm formation on hydrophilic (glass) and hydrophobic (polystyrene) abiotic surfaces, in the presence or absence of iron, and in the susceptibility profiles to antimicrobial agents. Futhermore, OxyR seem not to influence the pathogenicity of C. diphtheriae in C. elegans, since there was no significant difference in the nematode colonization and death assays with the strains analyzed, although a greater formation of the bagging effect has been observed in worms infected by the mutant strain. In conclusion, OxyR effects on C. diphtheriae virulence seem not to be solely related to the regulation of both oxidative and cold shock stress response, but are also associated with other clinically relevant processes that allow this pathogen to persist in the host tissues, despite inflammatory and cellular responses. |
id |
UERJ_4041002c58b71e1f801c330dfd78fe98 |
---|---|
oai_identifier_str |
oai:www.bdtd.uerj.br:1/20207 |
network_acronym_str |
UERJ |
network_name_str |
Biblioteca Digital de Teses e Dissertações da UERJ |
repository_id_str |
|
spelling |
Guaraldi, Ana Luíza de Mattoshttp://lattes.cnpq.br/8091118564093203Saliba, Alessandra Mattoshttp://lattes.cnpq.br/6134920105834158Rosa Ignacio, Ana Cláudia de Paulahttp://lattes.cnpq.br/7809403473011306Valente, Raphael do Carmohttp://lattes.cnpq.br/6551057809919379Gomes, Débora Leandro Ramahttp://lattes.cnpq.br/8456206846769267Vieira, Verônica Vianahttp://lattes.cnpq.br/0742408281665373http://lattes.cnpq.br/7398599068520311Cappelli, Elisabete Alvesb.cappelli@hotmail.com2023-08-24T12:11:35Z2018-08-16CAPPELLI, Elisabete Alves. Avaliação da influência de OxyR na resposta ao estresse e na virulência de Corynebacterium diphtheriae. 2018. 127 f. Tese (Doutorado em Microbiologia) – Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2018.http://www.bdtd.uerj.br/handle/1/20207Corynebacterium diphtheriae, the major etiological agent of diphtheria, has been associated to invasive infections, regardless of diphtheria toxin production. This fact suggests that others virulence factors, besides to the diphtheria toxin production, are involved in the pathogenicity of this microorganism. Several mechanisms of survival and dissemination of the microorganism, both in the host and in the environment, contribute to the bacterial infections pathogenesis. Amongst the pathogenic mechanisms, the response of C. diphtheriae to different stress responses still remain misunderstood. The aim of this study was to investigate the role of the OxyR, already described as an important regulator involved in the resistance and virulence of other bacterial species, in the C. diphtheriae pathogenesis. Therefore, the parental strains CDC-E8392 and the mutant (LDCIC-L2), unable to produce OxyR, were compared for gene expression and survival ability under stress conditions. In addition, both strains were compared for their pathogenic potential, through interaction with epithelial cells and macrophages, biofilm formation, interaction with plasma and extracellular matrix proteins assays and in vivo infection to C. elegans nematodes and in Swiss Webster mice. The results indicated that OxyR regulates negatively the catalase expression and response to H2O2. The interruption of expression of OxyR also modulated the expression of cspA and the resistance to oxidative stress generated by ozone. The mutant strain showed a significant reduction in the capacity of binding to fibronectin, collagen and fibrinogen. The influence of OxyR on the virulence properties of C. diphtheriae was also evidenced by ability of the mutant strain to survive in the intracytoplasmic compartment of human epithelial cells and macrophage and to induce a more evident inflammatory process in knee joint in mice. In addition, despite the cellular infection of respiratory cells by C. diphtheriae strains lead to increased production of ROS and RNS, the OxyR– mutant strain induced a significantly higher production of NO than the cells infected with the wild type strain. However, interruption of OxyR did not induce a significant difference in both biofilm formation on hydrophilic (glass) and hydrophobic (polystyrene) abiotic surfaces, in the presence or absence of iron, and in the susceptibility profiles to antimicrobial agents. Futhermore, OxyR seem not to influence the pathogenicity of C. diphtheriae in C. elegans, since there was no significant difference in the nematode colonization and death assays with the strains analyzed, although a greater formation of the bagging effect has been observed in worms infected by the mutant strain. In conclusion, OxyR effects on C. diphtheriae virulence seem not to be solely related to the regulation of both oxidative and cold shock stress response, but are also associated with other clinically relevant processes that allow this pathogen to persist in the host tissues, despite inflammatory and cellular responses.Corynebacterium diphtheriae, principal agente etiológico da difteria, vem sendo relacionado com quadros de infecções invasivas, independentemente da produção da toxina diftérica. Além disso, quadros de difteria clássica têm sido reportados mesmo em pacientes imunizados. Estes fatos sugerem que outros mecanismos de virulência, além da toxina, estejam envolvidos na patogenicidade deste microrganismo. Diversos mecanismos de sobrevivência e disseminação dos microrganismos, no hospedeiro e no ambiente, contribuem para a patogênese das infecções bacterianas. Dentre estes, aqueles envolvidos na resposta a situações de estresse ainda permanecem incompreendidos em C. diphtheriae. Diante disso, este estudo teve como objetivo investigar o papel do regulador transcricional OxyR, já descrito como importante regulador envolvido na resistência e virulência de outras espécies bacterianas, na patogênese de C. diphtheriae. Neste sentido, a cepa parental CDC-E8392 e a cepa mutante (LDCIC-L2), incapaz de produzir OxyR, foram comparadas quanto à expressão gênica e a capacidade de sobrevivência em condições de estresse. Além disso, foram comparadas quanto ao seu potencial patogênico, a partir de ensaios de interação celular, de formação de biofilme, de interação com proteínas plasmáticas e de matriz extracelular, e de infecção em modelos in vivo em nematódeo C. elegans e em camundongos. Os resultados indicaram que OxyR regula negativamente a expressão de catalase e a resposta ao H2O2, e parece estar envolvido também na expressão de cspA e na resistência ao estresse oxidativo gerado pelo ozônio. A cepa mutante apresentou uma redução significativa na capacidade de ligação à fibronectina, ao colágeno e ao fibrinogênio. A influência do OxyR nas propriedades de virulência de C. diphtheriae também foi evidenciada pela maior capacidade desse mutante em sobreviver no compartimento intracitoplasmático de células epiteliais humanas e macrófago e por, aparentemente, levar a um processo inflamatório mais evidente em articulação de membro posterior em camundongos. Ademais, apesar da infecção por ambas as cepas de C. diphtheriae, levar a uma produção aumentada de ERO e ERN pelas células epiteliais respiratórias, aquelas infectadas pela cepa mutante produziram significativamente mais NO do que as infectadas pela selvagem. No entanto, a interrupção do OxyR não induziu diferença significativa na formação de biofilme em superfícies abióticas hidrofílicas (vidro) e hidrofóbicas (poliestireno), em presença e ausência de ferro, e nos perfis de susceptibilidade a doze agentes antimicrobianos testados. Além disso, o OxyR parece não influenciar na patogenicidade em C. elegans, uma vez que não houve diferença significativa nos ensaios de colonização e morte do nematodo pelas cepas de C. diphtheriae analisadas, embora, tenha sido observado uma maior formação do efeito bagging em vermes infectados pela cepa mutante. Infere-se, portanto, que os efeitos do sistema OxyR sobre a virulência de C. diphtheriae parecem, não estar exclusivamente relacionados com a regulação de genes de resistência ao estresse, mas também a outros processos clinicamente relevantes que permitem a este patógeno permanecer nos tecidos do hospedeiro, independentemente das respostas inflamatória e celular do sistema imune.Submitted by Heloísa CB/A (helobdtd@gmail.com) on 2023-08-24T12:11:35Z No. of bitstreams: 1 Tese - Elisabete Alves Cappelli - 2018 - Completa.pdf: 3779508 bytes, checksum: 51cbcfe477d7ee254b21ed3edbb15ad4 (MD5)Made available in DSpace on 2023-08-24T12:11:35Z (GMT). No. of bitstreams: 1 Tese - Elisabete Alves Cappelli - 2018 - Completa.pdf: 3779508 bytes, checksum: 51cbcfe477d7ee254b21ed3edbb15ad4 (MD5) Previous issue date: 2018-08-16application/pdfporUniversidade do Estado do Rio de JaneiroPrograma de Pós-Graduação em MicrobiologiaUERJBrasilCentro Biomédico::Faculdade de Ciências MédicasC. diphtheriaeOxyROxidative stressStressVirulenceBiofilmC. diphtheriaeOxyREstresse oxidativoEstresse térmicoVirulênciaBiofilmeCIENCIAS BIOLOGICAS::MICROBIOLOGIA::MICROBIOLOGIA APLICADA::MICROBIOLOGIA MEDICAAvaliação da influência de OxyR na resposta ao estresse e na virulência de Corynebacterium diphtheriaeInfluence of OxyR in stress response and virulence of Corynebacterium diphtheriaeinfo: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 - Elisabete Alves Cappelli - 2018 - Completa.pdfTese - Elisabete Alves Cappelli - 2018 - Completa.pdfapplication/pdf3779508http://www.bdtd.uerj.br/bitstream/1/20207/2/Tese+-+Elisabete+Alves+Cappelli+-+2018+-+Completa.pdf51cbcfe477d7ee254b21ed3edbb15ad4MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-82123http://www.bdtd.uerj.br/bitstream/1/20207/1/license.txte5502652da718045d7fcd832b79fca29MD511/202072024-02-26 15:59:48.434oai: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:29032024-02-26T18:59:48Biblioteca Digital de Teses e Dissertações da UERJ - Universidade do Estado do Rio de Janeiro (UERJ)false |
dc.title.por.fl_str_mv |
Avaliação da influência de OxyR na resposta ao estresse e na virulência de Corynebacterium diphtheriae |
dc.title.alternative.eng.fl_str_mv |
Influence of OxyR in stress response and virulence of Corynebacterium diphtheriae |
title |
Avaliação da influência de OxyR na resposta ao estresse e na virulência de Corynebacterium diphtheriae |
spellingShingle |
Avaliação da influência de OxyR na resposta ao estresse e na virulência de Corynebacterium diphtheriae Cappelli, Elisabete Alves C. diphtheriae OxyR Oxidative stress Stress Virulence Biofilm C. diphtheriae OxyR Estresse oxidativo Estresse térmico Virulência Biofilme CIENCIAS BIOLOGICAS::MICROBIOLOGIA::MICROBIOLOGIA APLICADA::MICROBIOLOGIA MEDICA |
title_short |
Avaliação da influência de OxyR na resposta ao estresse e na virulência de Corynebacterium diphtheriae |
title_full |
Avaliação da influência de OxyR na resposta ao estresse e na virulência de Corynebacterium diphtheriae |
title_fullStr |
Avaliação da influência de OxyR na resposta ao estresse e na virulência de Corynebacterium diphtheriae |
title_full_unstemmed |
Avaliação da influência de OxyR na resposta ao estresse e na virulência de Corynebacterium diphtheriae |
title_sort |
Avaliação da influência de OxyR na resposta ao estresse e na virulência de Corynebacterium diphtheriae |
author |
Cappelli, Elisabete Alves |
author_facet |
Cappelli, Elisabete Alves b.cappelli@hotmail.com |
author_role |
author |
author2 |
b.cappelli@hotmail.com |
author2_role |
author |
dc.contributor.advisor1.fl_str_mv |
Guaraldi, Ana Luíza de Mattos |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/8091118564093203 |
dc.contributor.advisor-co1.fl_str_mv |
Saliba, Alessandra Mattos |
dc.contributor.advisor-co1Lattes.fl_str_mv |
http://lattes.cnpq.br/6134920105834158 |
dc.contributor.referee1.fl_str_mv |
Rosa Ignacio, Ana Cláudia de Paula |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/7809403473011306 |
dc.contributor.referee2.fl_str_mv |
Valente, Raphael do Carmo |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/6551057809919379 |
dc.contributor.referee3.fl_str_mv |
Gomes, Débora Leandro Rama |
dc.contributor.referee3Lattes.fl_str_mv |
http://lattes.cnpq.br/8456206846769267 |
dc.contributor.referee4.fl_str_mv |
Vieira, Verônica Viana |
dc.contributor.referee4Lattes.fl_str_mv |
http://lattes.cnpq.br/0742408281665373 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/7398599068520311 |
dc.contributor.author.fl_str_mv |
Cappelli, Elisabete Alves b.cappelli@hotmail.com |
contributor_str_mv |
Guaraldi, Ana Luíza de Mattos Saliba, Alessandra Mattos Rosa Ignacio, Ana Cláudia de Paula Valente, Raphael do Carmo Gomes, Débora Leandro Rama Vieira, Verônica Viana |
dc.subject.eng.fl_str_mv |
C. diphtheriae OxyR Oxidative stress Stress Virulence Biofilm |
topic |
C. diphtheriae OxyR Oxidative stress Stress Virulence Biofilm C. diphtheriae OxyR Estresse oxidativo Estresse térmico Virulência Biofilme CIENCIAS BIOLOGICAS::MICROBIOLOGIA::MICROBIOLOGIA APLICADA::MICROBIOLOGIA MEDICA |
dc.subject.por.fl_str_mv |
C. diphtheriae OxyR Estresse oxidativo Estresse térmico Virulência Biofilme |
dc.subject.cnpq.fl_str_mv |
CIENCIAS BIOLOGICAS::MICROBIOLOGIA::MICROBIOLOGIA APLICADA::MICROBIOLOGIA MEDICA |
description |
Corynebacterium diphtheriae, the major etiological agent of diphtheria, has been associated to invasive infections, regardless of diphtheria toxin production. This fact suggests that others virulence factors, besides to the diphtheria toxin production, are involved in the pathogenicity of this microorganism. Several mechanisms of survival and dissemination of the microorganism, both in the host and in the environment, contribute to the bacterial infections pathogenesis. Amongst the pathogenic mechanisms, the response of C. diphtheriae to different stress responses still remain misunderstood. The aim of this study was to investigate the role of the OxyR, already described as an important regulator involved in the resistance and virulence of other bacterial species, in the C. diphtheriae pathogenesis. Therefore, the parental strains CDC-E8392 and the mutant (LDCIC-L2), unable to produce OxyR, were compared for gene expression and survival ability under stress conditions. In addition, both strains were compared for their pathogenic potential, through interaction with epithelial cells and macrophages, biofilm formation, interaction with plasma and extracellular matrix proteins assays and in vivo infection to C. elegans nematodes and in Swiss Webster mice. The results indicated that OxyR regulates negatively the catalase expression and response to H2O2. The interruption of expression of OxyR also modulated the expression of cspA and the resistance to oxidative stress generated by ozone. The mutant strain showed a significant reduction in the capacity of binding to fibronectin, collagen and fibrinogen. The influence of OxyR on the virulence properties of C. diphtheriae was also evidenced by ability of the mutant strain to survive in the intracytoplasmic compartment of human epithelial cells and macrophage and to induce a more evident inflammatory process in knee joint in mice. In addition, despite the cellular infection of respiratory cells by C. diphtheriae strains lead to increased production of ROS and RNS, the OxyR– mutant strain induced a significantly higher production of NO than the cells infected with the wild type strain. However, interruption of OxyR did not induce a significant difference in both biofilm formation on hydrophilic (glass) and hydrophobic (polystyrene) abiotic surfaces, in the presence or absence of iron, and in the susceptibility profiles to antimicrobial agents. Futhermore, OxyR seem not to influence the pathogenicity of C. diphtheriae in C. elegans, since there was no significant difference in the nematode colonization and death assays with the strains analyzed, although a greater formation of the bagging effect has been observed in worms infected by the mutant strain. In conclusion, OxyR effects on C. diphtheriae virulence seem not to be solely related to the regulation of both oxidative and cold shock stress response, but are also associated with other clinically relevant processes that allow this pathogen to persist in the host tissues, despite inflammatory and cellular responses. |
publishDate |
2018 |
dc.date.issued.fl_str_mv |
2018-08-16 |
dc.date.accessioned.fl_str_mv |
2023-08-24T12:11:35Z |
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.citation.fl_str_mv |
CAPPELLI, Elisabete Alves. Avaliação da influência de OxyR na resposta ao estresse e na virulência de Corynebacterium diphtheriae. 2018. 127 f. Tese (Doutorado em Microbiologia) – Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2018. |
dc.identifier.uri.fl_str_mv |
http://www.bdtd.uerj.br/handle/1/20207 |
identifier_str_mv |
CAPPELLI, Elisabete Alves. Avaliação da influência de OxyR na resposta ao estresse e na virulência de Corynebacterium diphtheriae. 2018. 127 f. Tese (Doutorado em Microbiologia) – Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2018. |
url |
http://www.bdtd.uerj.br/handle/1/20207 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
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 instname:Universidade do Estado do Rio de Janeiro (UERJ) instacron:UERJ |
instname_str |
Universidade do Estado do Rio de Janeiro (UERJ) |
instacron_str |
UERJ |
institution |
UERJ |
reponame_str |
Biblioteca Digital de Teses e Dissertações da UERJ |
collection |
Biblioteca Digital de Teses e Dissertações da UERJ |
bitstream.url.fl_str_mv |
http://www.bdtd.uerj.br/bitstream/1/20207/2/Tese+-+Elisabete+Alves+Cappelli+-+2018+-+Completa.pdf http://www.bdtd.uerj.br/bitstream/1/20207/1/license.txt |
bitstream.checksum.fl_str_mv |
51cbcfe477d7ee254b21ed3edbb15ad4 e5502652da718045d7fcd832b79fca29 |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 |
repository.name.fl_str_mv |
Biblioteca Digital de Teses e Dissertações da UERJ - Universidade do Estado do Rio de Janeiro (UERJ) |
repository.mail.fl_str_mv |
bdtd.suporte@uerj.br |
_version_ |
1792352238531772416 |