title: The making of a gradient: IcsA (VirG) polarity in Shigella flexneri.
abstract: The generation and maintenance of subcellular organization in bacteria is critical for many cell processes and properties, including growth, structural integrity and, in pathogens, virulence. Here, we investigate the mechanisms by which the virulence protein IcsA (VirG) is distributed on the bacterial surface to promote efficient transmission of the bacterium Shigella flexneri from one host cell to another. The outer membrane protein IcsA recruits host factors that result in actin filament nucleation and, when concentrated at one bacterial pole, promote unidirectional actin-based motility of the pathogen. We show here that the focused polar gradient of IcsA is generated by its delivery exclusively to one pole followed by lateral diffusion through the outer membrane. The resulting gradient can be modified by altering the composition of the outer membrane either genetically or pharmacologically. The gradient can be reshaped further by the action of the protease IcsP (SopA), whose activity we show to be near uniform on the bacterial surface. Further, we report polar delivery of IcsA in Escherichia coli and Yersinia pseudotuberculosis, suggesting that the mechanism for polar delivery of some outer membrane proteins is conserved across species and that the virulence function of IcsA capitalizes on a more global mechanism for subcellular organization.
authors.affiliation: Department of Biochemistry, Stanford University School of Medicine, 279 West Campus Drive, Stanford, CA 94305-5307, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Robbins
authors.forename: D
authors.initials: D
authors.lastname: Monack
authors.forename: S J
authors.initials: SJ
authors.lastname: McCallum
authors.forename: A
authors.initials: A
authors.lastname: Vegas
authors.forename: E
authors.initials: E
authors.lastname: Pham
authors.forename: M B
authors.initials: MB
authors.lastname: Goldberg
authors.forename: J A
authors.initials: JA
authors.lastname: Theriot
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D016764:Cell Polarity; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004058:Diffusion; D005455:Fluorescent Antibody Technique; D008560:Membrane Fluidity; D012763:Shigella flexneri / Q000166:cytology / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D014157:Transcription Factors; C058483:virG protein, Shigella flexneri; C060971:SopA protein, Bacteria