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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2018.tde-22022018-113552
Document
Author
Full name
Lucas Ribeiro de Sousa Almeida
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2017
Supervisor
Committee
Mayer, Marcia Pinto Alves (President)
Baquerizo, Marina
Caldeira, Marinella Holzhausen
Elias Junior, Waldir Pereira
Saraiva, Luciana
Title in Portuguese
Adesina Aae de Aggregatibacter actinomycetemcomitans: envolvimento na adesão a proteínas da matriz extracelular, polimorfismo genético e resposta imune humoral.
Keywords in Portuguese
Aggregatibacter actinomycetemcomitans
Doença periodontal
Proteína de membrana externa
Proteínas autotransportadoras
Proteínas de matriz extracelular
Abstract in Portuguese
Aggregatibacter actinomycetemcomitans está associado à etiologia da periodontite agressiva localizada. A colonização de tecidos do hospedeiro é necessária para patogênese e a adesão é fundamental. A proteína autotransportada Aae faz a adesão da bactéria a células epiteliais gengivais. Proteínas autotransportadas de diferentes espécies apresentam múltiplas funções e podem ser antígenos vacinais na prevenção de infecções. Para entender o papel de Aae na ligação ao hospedeiro e efeito de anticorpos contra Aae, o polimorfismo de aae na região que codifica o domínio de ligação a células epiteliais foi determinado e relacionado à adesão a células epiteliais KB . Aae recombinante foi obtida, e a capacidade de ligação a proteínas da matriz extracelular e soro foi determinada em ensaios com a recombinante e com uma amostra deficiente na expressão de Aae obtida (ensaios comparativos com amostra selvagem). Títulos de IgG contra Aae em pacientes com periodontite agressiva e saudáveis foram determinados e relacionados à resposta humoral contra sorotipos de A. actinomycetemcomitans. Por fim, o efeito de anticorpos contra Aae e/ou seu domínio efetor, produzidos em modelo animal, foi determinado na inibição da adesão mediada por Aae e opsonização por fagócitos.
Title in English
Aae adhesin of A. actinomycetemcomitans: Implication in binding to extracellular matrix proteins, genetic polymorphisms and humoral immune response.
Keywords in English
Aggregatibacter actinomycetemcomitans
Autotransporter proteins
Extracellular matrix proteins
Outter membrane protein
Periodontal disease
Abstract in English
Aggregatibacter actinomycetemcomitans is related with etiology of localized aggressive periodontitis. Colonization of host tissues is necessary to pathogenesis and adhesion is essential. The autotransporter protein Aae mediates the adhesion of bacteria to gingival epithelial cells. Autotransporter proteins from different species have multiple functions and could be vaccine antigens to prevent infections. To understand the role of Aae in host interaction and the effect of antibodies against Aae, polymorphism of aae in codifying effector domain region of ligation to epithelial cells was determined and related with adhesion to these cells. Recombinant Aae was obtained and the ability of interaction with Extracellular matrix and serum proteins was determined through assays using the recombinant and an obtained defective sample in Aae expression (comparative assays with wild type). IgG titters against Aae were determined in patients with aggressive periodontitis and healthy and related to humoral response against A. actinomycetemcomitans serotypes. At last, the effect of antibodies against Aae and/or its effector domain, obtained in animal model, was determined in inhibition of adhesion to epithelial cells and macrophages oopsonization.
 
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Publishing Date
2018-02-22
 
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