title: The type III secretion system needle tip complex mediates host cell sensing and translocon insertion.
abstract: Type III secretion systems (T3SSs) are essential virulence determinants of many Gram-negative bacterial pathogens. The Shigella T3SS consists of a cytoplasmic bulb, a transmembrane region and a hollow 'needle' protruding from the bacterial surface. Physical contact with host cells initiates secretion and leads to assembly of a pore, formed by IpaB and IpaC, in the host cell membrane, through which proteins that facilitate host cell invasion are translocated. As the needle is implicated in host cell sensing and secretion regulation, its tip should contain components that initiate host cell contact. Through biochemical and immunological studies of wild-type and mutant Shigella T3SS needles, we reveal tip complexes of differing compositions and functional states, which appear to represent the molecular events surrounding host cell sensing and pore formation. Our studies indicate that the interaction between IpaB and IpaD at needle tips is key to host cell sensing, orchestration of IpaC secretion and its subsequent assembly at needle tips. This allows insertion into the host cell membrane of a translocation pore that is continuous with the needle.
authors: Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
authors: Andreas K J
authors: AK
authors: Veenendaal
authors: Julie L
authors: JL
authors: Hodgkinson
authors: Lynn
authors: L
authors: Schwarzer
authors: David
authors: D
authors: Stabat
authors: Sebastian F
authors: SF
authors: Zenk
authors: Ariel J
authors: AJ
authors: Blocker
mesh_terms: D000942:Antigens, Bacterial / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism* / Q000648:ultrastructure; D012634:Bodily Secretions / Q000502:physiology*; D015964:Gene Expression Regulation, Bacterial; D021381:Protein Transport; D012763:Shigella flexneri / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity / Q000502:physiology*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C087447:ipaB protein, Shigella; C092342:IpaC protein, Shigella