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Project grant
Title [sv]
Mekanismer bakom avdödningen av Francisella tularensis med speciellt fokus på reaktiva syreradikaler och järn och deras koppling till vaccin-medierat skydd
Title [en]
Mechanisms effectuating killing of Francisella tularensis with a special focus on reactrive oxygen species and iron and their relationship to vaccine-mediated protection
Abstract [sv]
The project will investigate the mechanisms effectuating killing of the highly virulent, intracellular bacterium Francisella tularensis with a special focus on its control of iron uptake and how it resists the cidal effects of reactive oxygen species. Our existing data indicate that an essential part of its strategy is to fine-tune the uptake of iron essential to its replication and many enzymatic functions but to avoid the detrimental effects of the Fenton reaction and we hypothesize that this is a key for its highly successful adaptation to the intracellular habitat. We will now further investigate the relationship between ROS and iron uptake and also investigate if this knowledge can be used to develop therapeutic strategies against F. tularensis. The roles of ROS and iron will also be investigated in several ex vivo mouse models to validate our existing in vitro findings. A special focus will be to delineate the bactericidal mechanisms of vaccine-mediated protection based on our novel vaccine candidates. Also, mechanisms and protective correlates identified in the mouse model will be compared to those of tularemia-vaccinated humans or former patients in order to identify correlates of protection against the disease. The latter part of the work will aim to generate sufficient data so that our best vaccine can be evaluated in human Phase 1 trials. There is need for an efficacious vaccine in endemic areas in Scandinavia since the annual incidence of tularemia is very high.
Principal InvestigatorSjöstedt, Anders
Coordinating organisation
Umeå University
2013-01-01 - 2015-12-31
National Category
Microbiology in the medical areaImmunology in the medical areaInfectious Medicine
DiVA, id: project:1210Project, id: 2012-03469_VR