SABDII · Staphylococcus aureus biofilm dynamics and innate immunity
7РП — „Хора“ (Действия „Мария Кюри“)
- Период
- 2010-09-01 → 2013-08-31
- Финансиране от ЕС
- 45 000 €
- Участници
- 1
- Схема
- MC-ERG
Линиите свързват координатора с партньорите.
Накратко на български
Взаимодействието между бактериалните биофилми на S. aureus и имунната система се анализира чрез примери като пептидите PSM, които разрушават мембраните на белите кръвни клетки. Това помага да се разбере как бактериите избягват защитата на организма при развитието на инфекцията.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Staphylococcus aureus biofilm dynamics and innate immunity
During this project the interaction of S. aureus biofilms and the human innate immune system was studied. Several in vitro biofilm growth models were set up, both static as well as flow cell biofilm cultures). Using these model systems, the different stages in biofilm development were characterized. For each system and biofilm stage the expression and secretion of immune evasion and immune stimulating molecules was measured. A highly interesting hit from these screenings were the S.aureus Phenol Soluble Modulins (PSMs). These small amphipatic peptides can stimulate the immune cells at low concentrations, but lyse these cells at higher concentrations by creating holes in the cellular membrane. The PSMs were studied in more detail, and their expression in biofilms and inside white blood cells was described in a paper in PlosPathogens (2012) and three follow-up papers in Cellular Microbiology, Infection and Immunity and JoVE (2013). In total 7 papers were published during the duration of the EU-ERG funded project. The setup of the biofilm flow cells in combination with the time lapse fluorescent imaging has resulted in a great opportunity for the fellow. He has established himself as an expert in this field and because of this was approached for several collaborations. One of these collaborations on Neisserial biofilms has already lead to a published Molecular Microbiology paper, with a second in manuscript in progress. The fellow has been able to firmly reintegrate in the Dutch microbiology community. Several collaborations were established with Utrecht University, Leiden UMC, Groningen University, UMCNijmegen. These collaborations resulted in published manuscripts and several more manuscripts in preparation Also a large number of international collaborations was set up, both directly assisting with the research as well as establishing a longer-term professional network essential for successful progression of the fellows career.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
During my postdoc at a marine biotechnology lab in Newcastle I experienced that bacteria growing in shakeflasks in the lab and bacteria in natural biofilms behave very differently. For instance, the global gene expression and production of secreted proteins is very different between these modes of growth. I would like to bring the knowledge and skills acquired there to a higher level by studying the interaction between a clinically relevant biofilm and host organism. To achieve this, I will study the dynamics of Staphylococcus aureus biofilms in interaction with the human innate immune system in the laboratory of Prof. van Strijp in Utrecht. S. aureus is a Gram-positive coccus that causes life threatening diseases and has become resistant against most antibiotics (MRSA). Our innate immune system is crucial in fighting S. aureus infections. Strikingly, S. aureus evades this defence line by production of small secreted proteins that repress this immune system. In many infections, S. aureus’ growth mode is generally considered to be biofilm-like. Using a novel, biofilm centred approach I will study the interaction between the innate immune system and S. aureus. By comparing planktonic growth with several biofilm stages using proteomic analysis, I will screen for novel immune evasion molecules that are expressed specifically during the biofilm mode of growth of S. aureus. The identified proteins will be studied further using deletion mutants in S. aureus and the proteins will be overexpressed in heterologous hosts, such as E. coli or B. subtilis. Using the mutant strains and the overproduced proteins, the specific interactions of these novel proteins with the innate immune system will be examined, both in vitro and in vivo. The identified molecules will be highly interesting drug targets against a problematic microbial pathogen
Оригинален текст от CORDIS (на английски).
Участници
- UNIVERSITAIR MEDISCH CENTRUM UTRECHT · UtrechtКоординаторНидерландия
Връзки
Данни: CORDIS, © Европейски съюз