Abstract
ABSTRACTBacterial pathogens exploit eukaryotic pathways for their own end. Upon ingestion, Salmonella enterica serovar Typhimurium passes through the stomach and then catalyzes its uptake across the intestinal epithelium. It survives and replicates in an acidic vacuole through the action of virulence factors secreted by a type three secretion system located on Salmonella pathogenicity island 2 (SPI-2). Two secreted effectors, SifA and SseJ, are sufficient for endosomal tubule formation, which modifies the vacuole and enables Salmonella to replicate within it. Two-color, superresolution imaging of the secreted virulence factor SseJ and tubulin revealed that SseJ formed clusters of conserved size at regular, periodic intervals in the host cytoplasm. Analysis of SseJ clustering indicated the presence of a pearling effect, which is a force-driven, osmotically sensitive process. The pearling transition is an instability driven by membranes under tension; it is induced by hypotonic or hypertonic buffer exchange and leads to the formation of beadlike structures of similar size and regular spacing. Reducing the osmolality of the fixation conditions using glutaraldehyde enabled visualization of continuous and intact tubules. Correlation analysis revealed that SseJ was colocalized with the motor protein kinesin. Tubulation of the endoplasmic reticulum is driven by microtubule motors, and in the present work, we describe how Salmonella has coopted the microtubule motor kinesin to drive the force-dependent process of endosomal tubulation. Thus, endosomal tubule formation is a force-driven process catalyzed by Salmonella virulence factors secreted into the host cytoplasm during infection.
Highlights
Bacterial pathogens exploit eukaryotic pathways for their own end
We examined the distribution of SseJ with respect to the late endosomal marker LAMP-1, tubulin, or kinesin, using two-color superresolution imaging
It is hypothesized that endosomal tubulation provides membrane and nutrients for the expanding vacuole, allowing Salmonella to replicate inside the vacuole during infection
Summary
Salmonella enterica serovar Typhimurium passes through the stomach and catalyzes its uptake across the intestinal epithelium It survives and replicates in an acidic vacuole through the action of virulence factors secreted by a type three secretion system located on Salmonella pathogenicity island 2 (SPI-2). Endosomal tubule formation is a force-driven process catalyzed by Salmonella virulence factors secreted into the host cytoplasm during infection. The present work reveals an unusual force-driven process, the pearling transition, which indicates that Salmonellainduced filaments are under force through the interactions of effector molecules with the motor protein kinesin. We used superresolution imaging to visualize the secreted effector SseJ during infection and discovered that in vivo forces transmitted by the motor protein kinesin are involved in endosomal trafficking induced by Salmonella. The pearling transition reveals a force-dependent process that drives endosomal tubulation, and here we identify kinesin as the motor that supplies this force [17]
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