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Infection and Immunity, March 2009, p. 996-1007, Vol. 77, No. 3
0019-9567/09/$08.00+0     doi:10.1128/IAI.01275-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Salmonella-Containing Vacuoles Display Centrifugal Movement Associated with Cell-to-Cell Transfer in Epithelial Cells{triangledown}

Jason Szeto,1,{dagger} Anton Namolovan,1 Suzanne E. Osborne,2 Brian K. Coombes,2 and John H. Brumell1,3*

Program in Cell Biology, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada,1 Department of Biochemistry and Biomedical Sciences and the Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario L8N 3Z5, Canada,2 Department of Molecular Genetics and Institute of Medical Science, University of Toronto, Toronto, Ontario M5S 1A8, Canada3

Received 17 October 2008/ Returned for modification 18 November 2008/ Accepted 15 December 2008

Intracellular Salmonella enterica serovar Typhimurium (serovar Typhimurium) occupies a Salmonella-containing vacuole (SCV) where bacterial effector proteins are secreted into the host cell using type III secretion systems (T3SS). Cytoskeletal motor proteins and T3SS-delivered effector proteins facilitate SCV positioning to juxtanuclear positions where bacterial replication occurs. Here, we show that this characteristic SCV positioning is not maintained by all SCVs during infection of HeLa cells. Notably, juxtanuclear SCV localization that occurs by 8 to 14 h postinfection is followed by significant centrifugal displacement of a subset of SCVs toward the host cell periphery by 24 h postinfection. This novel phenotype requires bacterial protein synthesis, a functional Salmonella pathogenicity island 2 (SPI-2)-encoded T3SS, intact microtubules, and kinesin-1 motor protein. Bacteria lacking PipB2, a kinesin-recruiting T3SS effector, did not exhibit centrifugal displacement and remained at juxtanuclear positions throughout 24 h of infection. While levels of the SPI-2 effectors PipB2 and SifA increased during 24 h postinfection, a corresponding decrease in levels of the SPI-1 T3SS effectors SipA and SopB, both known to mediate juxtanuclear SCV positioning, was observed. A fluorescence-based assay indicated that wild-type serovar Typhimurium transferred from infected to uninfected epithelial cells while strains deficient in SPI-2 T3SS secretion or PipB2 did not. Our results reveal a novel SCV phenotype implicated in the cell-to-cell spread of serovar Typhimurium during infection.

* Corresponding author. Mailing address: Program in Cell Biology, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada. Phone: (416) 813-7654, ext. 3555. Fax: (416) 813-5028. E-mail: john.brumell{at}sickkids.ca

{triangledown} Published ahead of print on 22 December 2008.

Editor: A. J. Bäumler

{dagger} Present address: Sanofi-Pasteur, Connaught Campus, 1755 Steeles Avenue West, Toronto, Ontario M2R 3T4, Canada.

Infection and Immunity, March 2009, p. 996-1007, Vol. 77, No. 3
0019-9567/09/$08.00+0     doi:10.1128/IAI.01275-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



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