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Previous issue date: 2011 / Além dos quadros de difteria clássica, Corynebacterium diphtheriae tem sido isolado de diversos processos infecciosos invasivos. Escassos são os trabalhos que procuram investigar in vivo os fatores que influenciam o estabelecimento e/ou a disseminação de amostras potencialmente invasoras de C. diphtheriae. Além disso, na literatura encontramos a descrição de inúmeros casos de um patógeno otencialmente perigoso para a população o Corynebacterium ulcerans, que se apresenta como um desafio para os órgãos de Saúde Pública brasileiros que somente recentemente o incluíram na rotina dos esquemas de isolamento e identificação. O presente estudo teve como objetivos gerais investigar processos invasivos desencadeados por amostras de C. diphtheriae e C. ulcerans potencialmente invasivas utilizando modelos experimentais em animais. Além de realizar a pesquisa de C. ulcerans em populações de caninos mantidos em instituição destinada ao abrigo de animais domésticos localizada na região metropolitana do Rio de Janeiro. Neste sentido foram desenvolvidos os seguintes objetivos específicos: (i) Avaliação do potencial artritogênico de cepas de origens diversas de C. diphtheriae e C. ulcerans através do modelo de artrite em murinos; (ii) Monitoramento em diferentes intervalos de tempo de microrganismos viáveis no sangue, pulmões, rins, fígado, baço, cérebro coração e articulações; (iii) Determinação dos níveis séricos de citocinas IL-6 e TNF-α decorrentes do processo infeccioso. Os resultados indicaram o modelo experimental de artrite em camundongos convencionais Swiss Webster infectados por via i.v. como mais adequado para a análise do potencial invasor das amostras. As 13 amostras de C. diphtheriae e C. ulcerans estudadas apresentaram potencial artritogênico em intensidades variadas, independente da capacidade de produção de DNAse, toxina diftérica e fosfolipase D (PLD). Dentre as amostras testadas, as de C... / Corynebacterium diphtheriae has been isolated from several invasive infectious diseases besides diphtheria disease. Few reports attempt to explain in vivo the factors influencing the establishment and / or the spread of potentially invasive strains of C. diphtheriae. Moreover, a large number of cases of a potentially infectious pathogen, Corynebacterium ulcerans, have been described worldwide, which can be seen as a challenge for Brazilian public health agencies which only recently included the isolation and identification of this pathogen in routine microbiological analysis. Therefore, this study aims to investigate general processes caused by invasive strains of C. diphtheriae and C. ulcerans using experimental models in animals. An additional objective is to conduct a research on C. ulcerans in populations of dogs kept in domestic animal shelter located in the metropolitan region of Rio de Janeiro. Thus, we have proposed the following specific objectives: (i) assess the arthritogenic potential of various C. diphtheriae and C. ulcerans strains by arthritis model in mice, (ii) monitor, at different time intervals, the presence of viable microorganisms in the blood, lungs, kidneys, liver, spleen, brain, heart and joints, (iii) determine serum levels of IL-6 and TNF-α under infectious process. The results indicated that the model of experimental infection in conventional Swiss Webster mice infected by IV route is suitable for the analysis of potential invasive strains. The 13 strains of C. diphtheriae and C. ulcerans showed arthritogenic potential on different levels, regardless of ability to produce DNase, diphtheria toxin and phospholipase D (PLD). Among the samples tested, C. diphtheriae isolated from cases of endocarditis and C. ulcerans isolated from infectious processes in humans and animals showed the greatest arthritogenic potential (> 50%) compared with the samples of C. diphtheriae isolated from classic diphtheria cases and C. ulcerans isolated from asymptomatic dogs. Histopathologic analysis showed the presence of subcutaneous edema, inflammatory reaction, damage to bone and synovial hypertrophy, consistent with a condition of severe arthritis for the samples considered more arthritogenic. Viable bacteria were recovered from the blood, kidneys, liver, spleen and joints. Both species caused polyarthritis, with wrists and ankles more often affected. The samples of C. ulcerans CDC-KC279 and 809 beside polyarthritis, preduced ulcerated lesions at the affected joints and nodose in the tail with extensive necrosis at the inoculation site (tail vein). The correlation between the arthritis and systemic levels of IL-6 and TNF-α was observed for the strains of C. ulcerans, with the exception of strain BR-AD22 that was unable to produce arthritis. In conclusion, our study showed a potential arthritogenic strain-dependent in C. diphtheriae and C. ulcerans indicating differences in virulence and invasive potential of these species independent of the production ability of diphtheria toxin and PLD.
| Identifer | oai:union.ndltd.org:IBICT/oai:www.arca.fiocruz.br:icict/8325 |
| Date | January 2011 |
| Creators | Dias, Alexandre Alves de Souza de Oliveira |
| Contributors | Vieira, Verônica Viana, Filippis, Ivano de, Hirata Junior, Raphael, Mattos-Guaraldi, Ana Luíza de, Villas Bôas, Maria Helena Simões, Mattos-Guaraldi, Ana Luíza de, Villas Bôas, Maria Helena Simões |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/doctoralThesis |
| Source | reponame:Repositório Institucional da FIOCRUZ, instname:Fundação Oswaldo Cruz, instacron:FIOCRUZ |
| Rights | info:eu-repo/semantics/openAccess |
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