title: FliZ regulates expression of the Salmonella pathogenicity island 1 invasion locus by controlling HilD protein activity in Salmonella enterica serovar typhimurium.
abstract: A prerequisite for Salmonella enterica to cause both intestinal and systemic disease is the direct injection of effector proteins into host intestinal epithelial cells via a type three secretion system (T3SS); the T3SS genes are carried on Salmonella pathogenicity island 1 (SPI1). These effector proteins induce inflammatory diarrhea and bacterial invasion. Expression of the SPI1 T3SS is tightly regulated in response to environmental signals through a variety of global regulatory systems. We have previously shown that three AraC-like regulators, HilD, HilC, and RtsA, act in a complex feed-forward regulatory loop to control the expression of the hilA gene, which encodes the direct regulator of the SPI1 structural genes. In this work, we characterize a major positive regulator of this system, the flagellar protein FliZ. Through genetic and biochemical analyses, we show that FliZ posttranslationally controls HilD to positively regulate hilA expression. This mechanism is independent of other flagellar components and is not mediated through the negative regulator HilE or through FliZ-mediated RpoS regulation. We demonstrate that FliZ controls HilD protein activity and not stability. FliZ regulates HilD in the absence of Lon protease, previously shown to degrade HilD. Indeed, it appears that FliZ, rather than HilD, is the most relevant target of Lon as it relates to SPI1 expression. Mutants lacking FliZ are significantly attenuated in their ability to colonize the intestine but are unaffected during systemic infection. The intestinal attenuation is partially dependent on SPI1, but FliZ has additional pleiotropic effects.
authors.affiliation: Department of Microbiology, University of Illinois, Urbana, Illinois 61801, USA.
authors.forename: Jessica E Cott
authors.initials: JE
authors.lastname: Chubiz
authors.forename: Yekaterina A
authors.initials: YA
authors.lastname: Golubeva
authors.forename: Dongxia
authors.initials: D
authors.lastname: Lin
authors.forename: Lucas D
authors.initials: LD
authors.lastname: Miller
authors.forename: James M
authors.initials: JM
authors.lastname: Slauch
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000378:metabolism*; D041981:Gastrointestinal Tract / Q000382:microbiology; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D012481:Salmonella Infections, Animal; D012486:Salmonella typhimurium / Q000235:genetics* / Q000472:pathogenicity; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014774:Virulence; D037521:Virulence Factors / Q000096:biosynthesis*
chemical_list: D001426:Bacterial Proteins; C119660:HilD protein, Salmonella typhimurium; C419942:Spi1 protein, Salmonella; D014157:Transcription Factors; D037521:Virulence Factors