title: Salmonella SPI1 effector SipA persists after entry and cooperates with a SPI2 effector to regulate phagosome maturation and intracellular replication.
abstract: Salmonellae employ two type III secretion systems (T3SSs), SPI1 and SPI2, to deliver virulence effectors into mammalian cells. SPI1 effectors, including actin-binding SipA, trigger initial bacterial uptake, whereas SPI2 effectors promote subsequent replication within customized Salmonella-containing vacuoles (SCVs). SCVs sequester actin filaments and subvert microtubule-dependent motors to migrate to the perinuclear region. We demonstrate that SipA delivery continues after Salmonella internalization, with dosage being restricted by host-mediated degradation. SipA is exposed on the cytoplasmic face of the SCV, from where it stimulates bacterial replication in both nonphagocytic cells and macrophages. Although SipA is sufficient to target and redistribute late endosomes, during infection it cooperates with the SPI2 effector SifA to modulate SCV morphology and ensure perinuclear positioning. Our findings define an unexpected additional function for SipA postentry and reveal precise intracellular communication between effectors deployed by distinct T3SSs underlying SCV biogenesis.
authors.affiliation: University of Cambridge, Department of Pathology, Tennis Court Road, Cambridge CB2 1QP, United Kingdom.
authors.forename: Lyndsey C
authors.initials: LC
authors.lastname: Brawn
authors.forename: Richard D
authors.initials: RD
authors.lastname: Hayward
authors.forename: Vassilis
authors.initials: V
authors.lastname: Koronakis
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism / Q000648:ultrastructure; D044404:Genomic Islands; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D022101:Microtubule-Organizing Center / Q000378:metabolism; D041681:NIH 3T3 Cells; D010588:Phagosomes / Q000378:metabolism / Q000382:microbiology / Q000648:ultrastructure; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012486:Salmonella typhimurium / Q000166:cytology / Q000472:pathogenicity* / Q000502:physiology*
chemical_list: D000199:Actins; D001426:Bacterial Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; C478165:PipB2 protein, Salmonella enterica; D011993:Recombinant Fusion Proteins; C440638:SPI-2 protein, Salmonella; C118287:SipA protein, Salmonella; C419942:Spi1 protein, Salmonella; C088597:invB protein, Salmonella; D016547:Kinesins