Use this URL to cite or link to this record in EThOS:
Title: The ubiquitin coat of cytosol-invading bacteria
Author: Werner, Emma Ilse
ISNI:       0000 0004 7968 4088
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2019
Availability of Full Text:
Access from EThOS:
Full text unavailable from EThOS. Thesis embargoed until 26 Oct 2025
Access from Institution:
Cytosol-invading Salmonella enterica serovar Typhimurium are labelled with a ubiquitin coat, which serves the dual purpose of targeting bacteria to autophagy-mediated degradation and locally inducing pro-inflammatory signalling. Importantly, the chain types and ubiquitylated substrates that constitute this ubiquitin coat are still poorly characterised. Here, I show that the ubiquitin coat of Salmonella is highly dynamic and undergoes significant compositional changes over the course of an infection. I also identify a novel ubiquitylated substrate on the bacterial surface. In contrast to Salmonella Typhimurium, a bacterium ill-adapted to cytosolic survival, Shigella flexneri is a professional cytosol-dwelling pathogen and evades targeting by host E3 ligases. In this work, I developed SPLINT Labelling, a novel tool to artificially induce ubiquitylation of S. flexneri by enforcing the recruitment of a Salmonella-targeting E3 ligase to the surface of Shigella. I demonstrate that SPLINT Labelling with LUBAC induces a M1-linked ubiquitin coat on S. flexneri and mediates the recruitment of the downstream antibacterial effectors P62, OPTINEURIN, NEMO and LC3. Nevertheless, SPLINT Labelling fails to inhibit proliferation of cytosolic S. flexneri. Overall, this work further defines the role of ubiquitylation for the detection and restriction of two different cytosol-invading pathogens.
Supervisor: Randow, Felix Sponsor: Medical Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
Keywords: Salmonella ; Ubiquitin ; Cell-autonomous immunity ; Shigella ; Autophagy ; SPLINT Labelling ; LUBAC