Projeto cofinanciado por:

Projecto nº: 029553

Referência do Projecto: PTDC/BIA-MOL/29553/2017 (POCI-01-0145-FEDER-029553)

Título: O impacto da dormência e da persistência de Staphylococcus epidermidis na resposta imunitária do hospedeiro

Montante envolvidos:

Investimento total: 237.515,12 €

IBMC-Instituto de Biologia Molecular e Celular – 117.505,25€

Apoio FEDER: 99.879,46€

Apoio OE: 17.625,79€

Localização do projecto: Porto, Portugal

Universidade do Minho – 112.209,87€

Apoio FEDER: 95.378,39€

Apoio OE: 16.831,48€

Localização do projecto: Braga, Portugal

Universidade do Porto – 7.800,00€

Apoio FEDER: 6.630,00€

Apoio OE: 1.1170,00€

Localização do projecto: Porto, Portugal

Sintese do projecto:

Staphylococcus epidermidis is a major inhabitant of healthy human skin and mucosae. However, it has emerged as one of the most common causes of medical device-related infections due to its capacity to form biofilms, being considered one of the leading causes of morbidity in Europe. The treatment of these infections is very complicated since bacteria within biofilms are highly tolerant to antibiotics and have the capacity to evade the host immune system attack. In the last years, this multidisciplinary team, which includes microbiologists, molecular biologists and immunologists has significantly contributed for the understanding of S. epidermis persistence. Studying S. epidermidis biofilm cells transcriptome, under different environmental conditions, it was possible to identify genes potentially involved in bacterium survival in the host, namely, genes involved in the induction of a dormant state. This state has been associated with increased tolerance to antibiotics but also with the ability of biofilm cells to evade the hostimmune system. The construction of mutant strains is, however, essential to confirm the role of the identified genes.

This will allow us to determine the molecular mechanisms involved in the pathogenesis of S. epidermidis and will help to conceive new and more directed strategies for the treatment of these infections. Hence, this project aims to characterize the role of the genes previously associated with S. epidermidis biofilm cells survival in the host and in the emergence of dormant cells, through the construction of mutants for those genes and evaluating their capacity to: 1) survive in the presence of host immune factors (using ex vivo human models and in vitro mouse models);2) survive to antibiotic therapy; 3) form biofilms and 4) generate dormant cells. The mutant strains constructed will be characterized using colony forming unit counting, flow cytometry and confocal microscopy. In addition, the host response to the presence of the mutant strains will be characterized using the models referred above. The function of different leukocytes populations stimulated with the mutant strains generated will be evaluated by flow cytometry and cell sorting, ELISA and ELISpot among other general immunology techniques. Thus, with the characterization of the phenotype of the mutant strains and the response of the host, it is expected to gain a better understanding of the biological processes that makes the harmless S. epidermidis one of the major pathogenic agents involved in the emergence of nosocomial infections.

Galeria de fotos do projeto

 

 


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