title: Shigella IpaD has a dual role: signal transduction from the type III secretion system needle tip and intracellular secretion regulation.
abstract: Type III secretion systems (T3SSs) are protein injection devices essential for the interaction of many Gram-negative bacteria with eukaryotic cells. While Shigella assembles its T3SS when the environmental conditions are appropriate for invasion, secretion is only activated after physical contact with a host cell. First, the translocators are secreted to form a pore in the host cell membrane, followed by effectors which manipulate the host cell. Secretion activation is tightly controlled by conserved T3SS components: the needle tip proteins IpaD and IpaB, the needle itself and the intracellular gatekeeper protein MxiC. To further characterize the role of IpaD during activation, we combined random mutagenesis with a genetic screen to identify ipaD mutant strains unable to respond to host cell contact. Class II mutants have an overall defect in secretion induction. They map to IpaD's C-terminal helix and likely affect activation signal generation or transmission. The Class I mutant secretes translocators prematurely and is specifically defective in IpaD secretion upon activation. A phenotypically equivalent mutant was found in mxiC. We show that IpaD and MxiC act in the same intracellular pathway. In summary, we demonstrate that IpaD has a dual role and acts at two distinct locations during secretion activation.
authors.affiliation: School of Cellular & Molecular Medicine, University of Bristol, University Walk, Bristol BS8 1TD, UK.
authors.forename: A Dorothea
authors.initials: AD
authors.lastname: Roehrich
authors.forename: Enora
authors.initials: E
authors.lastname: Guillossou
authors.forename: Ariel J
authors.initials: AJ
authors.lastname: Blocker
authors.forename: Isabel
authors.initials: I
authors.lastname: Martinez-Argudo
mesh_terms: D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D058947:Bacterial Secretion Systems; D004252:DNA Mutational Analysis; D015964:Gene Expression Regulation, Bacterial; D008958:Models, Molecular; D016296:Mutagenesis; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D012763:Shigella flexneri / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D015398:Signal Transduction; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; C095770:IpaD protein, Shigella flexneri; D050505:Mutant Proteins; D037521:Virulence Factors