title: Role for myosin II in regulating positioning of Salmonella-containing vacuoles and intracellular replication.
abstract: Salmonella enterica serovar Typhimurium grows within host cells in a permissive compartment termed the Salmonella-containing vacuole (SCV). These bacteria use two distinct type III secretion systems (T3SS) to deliver virulence proteins (effectors) into cells. Effectors secreted by the Salmonella pathogenicity island 1 (SPI-1)-encoded T3SS mediate invasion and early SCV maturation steps, while those secreted by the SPI-2 T3SS affect the SCV at later stages postinfection. Some SPI-2 effectors modulate microtubule motor activity on the SCV. Here, we show that the actin-based motor myosin II also affects SCV dynamics during infection. Following invasion, myosin II is required for SCV positioning near the nucleus of host cells. Later, myosin II counteracts the activities of the SPI-2 effectors PipB2 and SseJ to maintain SCV positioning and stability, respectively. Myosin II activity was required for maximal bacterial growth in macrophages. Rho kinase activity was required for SCV positioning. The effector SopB, a known activator of Rho GTPases, was found to be required for SCV positioning, and transfection of cells with SopB was sufficient to induce myosin II phosphorylation. These studies reveal a novel role for myosin II in controlling SCV dynamics during infection and suggest that SopB activates myosin II.
authors.affiliation: Cell Biology Program, Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Wasylnka
authors.forename: Malina A
authors.initials: MA
authors.lastname: Bakowski
authors.forename: Jason
authors.initials: J
authors.lastname: Szeto
authors.forename: Maikke B
authors.initials: MB
authors.lastname: Ohlson
authors.forename: William S
authors.initials: WS
authors.lastname: Trimble
authors.forename: Samuel I
authors.initials: SI
authors.lastname: Miller
authors.forename: John H
authors.initials: JH
authors.lastname: Brumell
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D002467:Cell Nucleus; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology; D006801:Humans; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D024462:Myosin Type II / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000166:cytology / Q000472:pathogenicity / Q000502:physiology*; D014617:Vacuoles / Q000187:drug effects / Q000382:microbiology*; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D006576:Heterocyclic Compounds, 4 or More Rings; C472645:blebbistatin; D054460:rho-Associated Kinases; C489224:SopB protein, Salmonella; D024462:Myosin Type II