The interaction dynamics of a negative feedback loop regulates flagellar number in Salmonella enterica serovar Typhimurium

Abstract

Each Salmonella enterica serovar Typhimurium cell produces a discrete number of complete flagella. Flagellar assembly responds to changes in growth rates through FlhD4C2 activity. FlhD4C2 activity is negatively regulated by the type 3 secretion chaperone FliT. FliT is known to interact with the flagellar filament cap protein FliD as well as components of the flagellar type 3 secretion apparatus. FliD is proposed to act as an anti-regulator, in a manner similar to FlgM inhibition of σ28 activity. We have found that efficient growth-dependent regulation of FlhD4C2 requires FliT regulation. In turn, FliD regulation of FliT modulates the response. We also show that, unlike other flagellar-specific regulatory circuits, deletion of fliT or fliD did not lead to an all-or-nothing response in FlhD4C2 activity. To investigate why, we characterized the biochemical interactions in the FliT FliD FlhD4C2 circuit. When FlhD4C2 was not bound to DNA, FliT disrupted the FlhD4C2 complex. Interestingly, when FlhD4C2 was bound to DNA it was insensitive to FliT regulation. This suggests that the FliT circuit regulates FlhD4C2 activity by preventing the formation of the FlhD4C2:DNA complex. Our data would suggest that this level of endogenous regulation of FlhD4C2 activity allows the flagellar system to efficiently respond to external signals. © 2010 Blackwell Publishing Ltd.