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Title [sv]
Rollerna av och relationerna mellan järnreglering, skydd mot reaktiva syreradikaler och virulens hos Francisella tularensis
Title [en]
The roles of and relationships between iron regulation, resistance to reactive oxygen species and the virulence of Francisella tularensis
Abstract [sv]
Francisella tularensis is an extremely virulent, intracellular pathogen and there are marked but unexplained virulence differences among its subspecies. Based on our existing results, we propose the novel hypothesis that resistance to reactive oxygen species (ROS) together with unique iron uptake mechanisms form a highly specialized adaptation of F. tularensis to the intracellular milieu. We will define how F. tularensis strains can utilize various forms of iron sources. We will identify the genes essential for iron uptake and ROS detoxification by use of > 700 transposon mutants and some 20 defined mutants. A major virulence mutant has markedly impaired utilization of transferrin. Using whole-genome microarrays, we will define the F. tularensis iron-dependent core gene modulon and the Fur regulon and also identify how these overlap with the genes activated in response to ROS. We hypothesize that F. tularensis encounters a microaerophilic milieu intracellularly and will by using microarrays analyze how F. tularensis adapts to such conditions and if it affects iron uptake or resistance to ROS. We will validate findings from the in vitro work by determining the roles of specific genes intracellularly and in vivo by IVIS. The work will identify mechanisms that reveal how intracellular bacteria solve the enigma of obtaining iron in the hostile intracellular environment. Our data indicate that understanding the mechanisms will help to explain the high virulence of F. tularensis.
Principal InvestigatorSjöstedt, Anders
Coordinating organisation
Umeå University
Funder
Period
2010-01-01 - 2012-12-31
Identifiers
DiVA, id: project:990Project, id: 2009-03496_VR

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