title: 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 FlhD(4) C(2) activity. FlhD(4) C(2) 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 σ(28) activity. We have found that efficient growth-dependent regulation of FlhD(4) C(2) 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 FlhD(4) C(2) activity. To investigate why, we characterized the biochemical interactions in the FliT : FliD :  FlhD(4) C(2) circuit. When FlhD(4) C(2) was not bound to DNA, FliT disrupted the FlhD(4) C(2) complex. Interestingly, when FlhD(4) C(2) was bound to DNA it was insensitive to FliT regulation. This suggests that the FliT circuit regulates FlhD(4) C(2) activity by preventing the formation of the FlhD(4) C(2) :DNA complex. Our data would suggest that this level of endogenous regulation of FlhD(4) C(2) activity allows the flagellar system to efficiently respond to external signals.
authors.affiliation: Centre for Bacterial Cell Biology, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Christine
authors.initials: C
authors.lastname: Aldridge
authors.forename: Kritchai
authors.initials: K
authors.lastname: Poonchareon
authors.forename: Supreet
authors.initials: S
authors.lastname: Saini
authors.forename: Thomas
authors.initials: T
authors.lastname: Ewen
authors.forename: Alexandra
authors.initials: A
authors.lastname: Soloyva
authors.forename: Christopher V
authors.initials: CV
authors.lastname: Rao
authors.forename: Katsumi
authors.initials: K
authors.lastname: Imada
authors.forename: Tohru
authors.initials: T
authors.lastname: Minamino
authors.forename: Phillip D
authors.initials: PD
authors.lastname: Aldridge
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D005407:Flagella / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D011485:Protein Binding; D012486:Salmonella typhimurium / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins