Biofilms are commonly defined as a community of bacteria attached to a surface and surrounded by a matrix of extrapolymeric substances (such as proteins, lipids, DNA and/or polysaccharides). The biofilm lifecycle is currently described in 4 main stages: 1) adhesion, 2) accumulation, 3) maturation and 4) disassembly. Biofilm disassembly, which refers to the release of bacterial from the biofilm into the involving environment, is the less understood of all steps despite its role in the establishment of important secondary biofilm-related infections. It is now clear that the widespread application of indwelling medical devices has tremendously expanded the situations wherein Staphylococcus epidermidis, by growing attached to these devices, can infect patients and cause a biofilm-originated disease. S. epidermidis biofilm infections are a significant burden to the public health system, with estimated costs of treatment over billions dollars per year, just in the USA. Biofilms have been extensively studied in the past by this research team, in particular those formed by S. epidermidis. In our most recent work, we found that S. epidermidis biofilm released cells represent a distinct phenotype and that this subpopulation of cells interacts differently with the murine immune system, when compared with their planktonic counterparts. Importantly, the release of cells from the biofilm into the bloodstream has been suggested as the cause of serious acute infections, but little studies have addressed this group of S. epidermidis cells. Based in our novel findings, we proposed this exploratory project aiming to identify the most relevant mechanisms involved in immune evasion or immune tolerance of S. epidermidis biofilm-released cells, using a transcriptomic approach. We will first use RNA sequencing technology to identify the pool of genes significantly up- or down-regulated in an ex vivo human blood model, and then confirm this screening with qPCR analysis. Genes with particular involvement in bacterium survival and immune evasion and tolerance will then be quantified in distinct clinical and commensal S epidermidis isolates, that were previously genotipically and phenotipically characterized. The identification of genes uniquely expressed upon contact with human blood components will allow us to uncover the strategies employed by this bacterium to overcome the host first line of defense and cause systemic infections. The multidisciplinary team involved on this project gathers specialists from clinical and applied sciences, and these two points of view are expected to strengthen the present proposal. The team skills on the fields of basic and applied immunology, microbial pathogenic biofilms, molecular microbiology and transcriptomics is expected to significantly contribute to understand the role of S. epidermidis biofilm-released cells on disease.

• ID do projeto/bolsa

  133123

• Referência

  EXPL/BIA-MIC/0101/2013

• FundRef URI

  http://www.fct.pt/apoios/projectos/consulta/vglobal_projecto.phtml.en?idProjecto=133123&idElemConcurso=8168

• Financiador

  FCT - Fundação para a Ciência e a Tecnologia, I.P.

• País do financiador

  Portugal

• Programa de financiamento

  5876-PPCDTI

• Valor financiado

  49,932.00 €

• Data de início

  2014-03-01

• Data de fim

  2015-08-31