Envolvimento de proteínas de membrana de Leptospira interrogans nos mecanismos de evasão e invasão do hospedeiro.

Siqueira, Gabriela Hase

doi:10.11606/T.87.2014.tde-08122014-124353

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Doctoral Thesis

DOI

https://doi.org/10.11606/T.87.2014.tde-08122014-124353

Document

Doctoral Thesis

Author

Siqueira, Gabriela Hase (Catálogo USP)

Full name

Gabriela Hase Siqueira

Institute/School/College

Interunidades em Biotecnologia

Knowledge Area

Biotechnology

Date of Defense

2014-06-27

Published

São Paulo, 2014

Supervisor

Nascimento, Ana Lucia Tabet Oller do (Catálogo USP)

Committee

Nascimento, Ana Lucia Tabet Oller do (President)
Gomez, José Gregorio Cabrera
Guth, Beatriz Ernestina Cabilio
Huenuman, Nilton Erbet Lincopan
Ruiz, Rita de Cássia

Title in Portuguese

Envolvimento de proteínas de membrana de Leptospira interrogans nos mecanismos de evasão e invasão do hospedeiro.

Keywords in Portuguese

Leptospira
Leptospirose
Mecanismos de patogenicidade
Patogenia
Proteínas recombinantes

Abstract in Portuguese

Leptospirose é uma zoonose mundial que causa grandes prejuízos econômicos e sociais. Os mecanismos de patogenicidade da leptospira ainda não estão totalmente elucidados. Nesse trabalho foi avaliado o papel de três proteínas hipotéticas de superfície na patogenia da leptospirose: LIC11009, LIC11360 e LIC11975. Os genes foram clonados a partir do DNA da L. interrogans sorovar Copenhageni e as proteínas recombinantes foram purificadas por cromatografia de afinidade. RT-qPCR mostrou a transcrição dos genes em leptospiras. As proteínas recombinantes reagiram com soro de humanos diagnosticados com leptospirose. rLIC11009 induziu somente resposta imune Th1 em camundongos, enquanto que rLIC11360 e rLIC11975 induziram resposta Th1 e Th2. As três proteínas recombinantes se ligaram à laminina e plasminogênio, enquanto rLIC11360 e rLIC11975 também se ligaram à fibronectina plasmática e fibrinogênio. Em adição, rLIC11360 se ligou ainda aos reguladores do sistema complemento fator H e C4BP. Os resultados sugerem que as proteínas estudadas podem auxiliar a leptospira a evadir e invadir o hospedeiro.

Title in English

Involvement of Leptospira interrogans membrane proteins in evasion and invasion mechanisms of the host.

Keywords in English

Leptospira
Leptospirosis
Pathogenesis
Pathogenicity mechanisms
Recombinant proteins

Abstract in English

Leptospirosis is a worldwide zoonosis that causes great economic and social losses. The pathogenic mechanisms of leptospira are not yet fully elucidated. In this study we evaluated the role of three hypothetical surface proteins in the leptospiral pathogenesis: LIC11009, LIC11360 and LIC11975. Genes were cloned from DNA of L. interrogans serovar Copenhageni and the recombinant proteins were purified by affinity chromatography. RT - qPCR data have shown that the genes are fully transcribed in leptospires. Recombinant proteins reacted with sera from humans diagnosed with leptospirosis. rLIC11009 induced Th1 immune response in mice, whereas rLIC11360 and rLIC11975 promoted both Th1 and Th2. The three recombinant proteins interacted with laminin and plasminogen while, rLIC11360 and rLIC11975, also interacted with plasma fibronectin and fibrinogen. In addition, rLIC11360 interacted with the complement regulators factor H and C4BP. These results suggest that the proteins tested can help leptospires to evade and invade the host.

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Publishing Date

2014-12-10

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