The pearling transition provides evidence of force-driven endosomal tubulation during Salmonella infection

  • Bacterial 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.

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Author:Yunfeng Gao, Christoph Klaus Spahn, Mike HeilemannORCiDGND, Linda J. Kenney
Pubmed Id:
Parent Title (English):mBio
Publisher:American Society for Microbiology
Place of publication:Washington, DC
Contributor(s):Tarek Msadek
Document Type:Article
Year of Completion:2018
Date of first Publication:2018/06/19
Publishing Institution:Universit├Ątsbibliothek Johann Christian Senckenberg
Release Date:2018/07/17
Tag:Salmonella Typhimurium; Salmonella-induced filaments; SseJ; endosomal tubulation; kinesin; pearling transition; superresolution microscopy
Issue:3, e01083-18
Page Number:10
First Page:1
Last Page:10
ASM publishes mBio articles under the Creative Commons Attribution license. Starting in 2016, articles are covered under a Creative Commons Attribution 4.0 International license.The author(s) retains copyright under this license. Others may adapt, reorganize, and build upon the published work for noncommercial purposes, as long as credit to the author and original article is given, and the new work, which includes the previously published content, is licensed under identical terms.
Institutes:Biochemie, Chemie und Pharmazie / Biochemie und Chemie
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0