Contribution of Fdh3 and @entity9446 to XXXX Redox State, Stress Adaptation and Virulence in @entity5132 .

@entity1 @entity5568 @entity1568 @entity9492 @entity12557 @entity19 @entity26 @entity2041 @entity406 @entity1110 @entity5132 @entity6172 @entity281 @entity9446 @entity3655
UNASSIGNED: The major fungal pathogen of @entity1 , @entity5132 , is exposed to reactive @entity1568 and @entity26 species following phagocytosis by host immune cells. In response to these toxins, this fungus activates potent anti-stress responses that include scavenging of reactive nitrosative and oxidative species via the @entity2041 system. Here we examine the differential roles of two @entity2041 recycling enzymes in redox homeostasis, stress adaptation and virulence in @entity5132 : @entity2041 reductase ( @entity9446 ) and the @entity12557 reductase (GSNOR), Fdh3. We show that the @entity1110 -dependent @entity9446 recycles @entity9492 to @entity6172 , is induced in response to oxidative stress and is required for resistance to macrophage killing. @entity9446 deletion increases the sensitivity of @entity5132 cells to @entity5568 , but not to @entity406 or NO. In contrast, Fdh3 detoxifies GSNO to @entity9492 and @entity3655 , and FDH3 inactivation delays NO adaptation and increases NO sensitivity. @entity5132 fdh3    cells are also sensitive to @entity406 , suggesting that Fdh3 also contributes to @entity406 detoxification. FDH3 is induced in response to nitrosative, oxidative and @entity406 stress, and fdh3   cells are more sensitive to killing by macrophages. Both @entity9446 and Fdh3 contribute to virulence in the Galleria mellonella and @entity19 models of @entity281 . We conclude that @entity9446 and Fdh3 play differential roles during the adaptation of @entity5132 cells to oxidative, nitrosative and @entity406 stress, and hence during the colonisation of the host. Our findings emphasise the importance of the @entity2041 system and the maintenance of intracellular redox homeostasis in this major pathogen.
