Liposomes recruit IpaC to the Shigella flexneri type III secretion apparatus needle as a final step in secretion induction.
Shigella flexneri contact with enterocytes induces a burst of protein secretion via its type III secretion apparatus (TTSA) as an initial step in cellular invasion. We have previously reported that IpaD is positioned at the TTSA needle tip (M. Espina et al., Infect. Immuno. 74:4391-4400, 2006). From this position, IpaD senses small molecules in the environment to control the presentation of IpaB to the needle tip. This step occurs without type III secretion induction or IpaC recruitment to the S. flexneri surface. IpaC is then transported to the S. flexneri surface when target cell lipids are added, and this event presumably mimics host cell contact. Unlike IpaB mobilization, IpaC surface presentation is closely linked to secretion induction. This study demonstrates that sphingomyelin and cholesterol are key players in type III secretion induction and that they appear to interact with IpaB to elicit IpaC presentation at the TTSA needle tip. Furthermore, IpaB localization at the needle tip prior to membrane contact provides the optimal set of conditions for host cell invasion. Thus, the S. flexneri type III secretion system can be induced in a stepwise manner, with the first step being the stable association of IpaD with the needle tip, the second step being the sensing of small molecules by IpaD to mobilize IpaB to the tip, and the third step being the interaction of lipids with IpaB to induce IpaC localization at the needle tip concomitant with translocon insertion into the host membrane and type III secretion induction.
Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045, USA.
Chelsea R
CR
Epler
Nicholas E
NE
Dickenson
Andrew J
AJ
Olive
Wendy L
WL
Picking
William D
WD
Picking
D000942:Antigens, Bacterial / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008081:Liposomes / Q000378:metabolism*; D021381:Protein Transport; D012763:Shigella flexneri / Q000378:metabolism*; D013109:Sphingomyelins / Q000378:metabolism
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D008081:Liposomes; D013109:Sphingomyelins; C087447:ipaB protein, Shigella; C092342:IpaC protein, Shigella; D002784:Cholesterol