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Salmonella Translocated Effectors Recruit OSBP1 to the Phagosome to Promote Vacuolar Membrane Integrity

48 Pages Posted: 5 Jun 2018 Sneak Peek Status: Under Review

See all articles by Anna M. Kolodziejek

Anna M. Kolodziejek

University of Washington - Department of Laboratory Medicine and Microbiology

Melissa A. Altura

University of Washington - Department of Laboratory Medicine and Microbiology

Junping Fan

University of Washington - Department of Laboratory Medicine and Microbiology

Erik M. Petersen

University of Washington - Department of Laboratory Medicine and Microbiology

Matthew Cook

University of Washington - Department of Biochemistry

Peter S. Brzovic

University of Washington - Department of Biochemistry

Samuel I. Miller

University of Washington - Department of Laboratory Medicine and Microbiology

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Abstract

Intracellular Salmonella use a type III secretion system (TTSS) to translocate effector proteins across the phagosome membrane to promote vacuole membrane tubulation, resulting in intracellular survival. This work demonstrates that the effector SseJ binds the eukaryotic lipid transporter oxysterol binding protein 1 (OSBP1). SseJ directs OSBP1 to the endosomal compartment in a manner dependent on the TTSS located on Salmonella pathogenicity island 2 (SPI2) and is mediated by both SseJ and another OSBP1-binding SPI2 translocated effector, the deubiquitinase SseL. Only deletion of both SseJ and SseL reduced vacuolar integrity with increased bacteria released into the eukaryotic cytoplasm, indicating that their combined activities are necessary for vacuole membrane stability. Cells deleted for the OSBP1-binding proteins VAPA/B also demonstrate loss of vacuole integrity, consistent with the hypothesis that OSBP1 recruitment is required to provide membrane for a vacuole undergoing endosomal tubulation, cholesterol esterification, and other SPI2-mediated alterations that promote Salmonellae intracellular survival.

Suggested Citation

Kolodziejek, Anna M. and Altura, Melissa A. and Fan, Junping and Petersen, Erik M. and Cook, Matthew and Brzovic, Peter S. and Miller, Samuel I., Salmonella Translocated Effectors Recruit OSBP1 to the Phagosome to Promote Vacuolar Membrane Integrity (2018). Available at SSRN: https://ssrn.com/abstract=3188415 or http://dx.doi.org/10.2139/ssrn.3188415
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Anna M. Kolodziejek (Contact Author)

University of Washington - Department of Laboratory Medicine and Microbiology

1705 NE Pacific St. HSB K-343
Box 357735
Seattle, WA 98195-7735
United States

Melissa A. Altura

University of Washington - Department of Laboratory Medicine and Microbiology

1705 NE Pacific St. HSB K-343
Box 357735
Seattle, WA 98195-7735
United States

Junping Fan

University of Washington - Department of Laboratory Medicine and Microbiology

1705 NE Pacific St. HSB K-343
Box 357735
Seattle, WA 98195-7735
United States

Erik M. Petersen

University of Washington - Department of Laboratory Medicine and Microbiology

1705 NE Pacific St. HSB K-343
Box 357735
Seattle, WA 98195-7735
United States

Matthew Cook

University of Washington - Department of Biochemistry

1705 NE Pacific St.
Health Sciences Building, J-Wing, Room J405
Seattle, WA 98195-735
United States

Peter S. Brzovic

University of Washington - Department of Biochemistry

1705 NE Pacific St.
Health Sciences Building, J-Wing, Room J405
Seattle, WA 98195-735
United States

Samuel I. Miller

University of Washington - Department of Laboratory Medicine and Microbiology ( email )

1705 NE Pacific St. HSB K-343
Box 357735
Seattle, WA 98195-7735
United States

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