Linear ubiquitination of cytosolic Salmonella Typhimurium activates NF-[kappa]B and restricts bacterial proliferation
Ubiquitination of invading Salmonella Typhimurium triggers autophagy of cytosolic bacteria and restricts their spread in epithelial cells. Ubiquitin (Ub) chains recruit autophagy receptors such as p62/SQSTM1, NDP52/CALCOCO and optineurin (OPTN), which initiate the formation of double-membrane autoph...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
08 May 2017
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| In: |
Nature microbiology
Year: 2017, Volume: 2, Issue: 7 |
| ISSN: | 2058-5276 |
| DOI: | 10.1038/nmicrobiol.2017.66 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1038/nmicrobiol.2017.66 Verlag, Volltext: https://www.nature.com/articles/nmicrobiol201766 
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| Author Notes: | Sjoerd J.L. van Wijk, Franziska Fricke, Lina Herhaus, Jalaj Gupta, Katharina Hötte, Francesco Pampaloni, Paolo Grumati, Manuel Kaulich, Yu-shin Sou, Masaaki Komatsu, Florian R. Greten, Simone Fulda, Mike Heilemann, &Ivan Dikic |
| Summary: | Ubiquitination of invading Salmonella Typhimurium triggers autophagy of cytosolic bacteria and restricts their spread in epithelial cells. Ubiquitin (Ub) chains recruit autophagy receptors such as p62/SQSTM1, NDP52/CALCOCO and optineurin (OPTN), which initiate the formation of double-membrane autophagosomal structures and lysosomal destruction in a process known as xenophagy. Besides this, the functional consequences and mechanistic regulation of differentially linked Ub chains at the host-Salmonella interface have remained unexplored. Here, we show, for the first time, that distinct Ub chains on cytosolic S. Typhimurium serve as a platform triggering further signalling cascades. By using single-molecule localization microscopy, we visualized the balance and nanoscale distribution pattern of linear (M1-linked) Ub chain formation at the surface of cytosolic S. Typhimurium. In addition, we identified the deubiquitinase OTULIN as central regulator of these M1-linked Ub chains on the bacterial coat. OTULIN depletion leads to enhanced formation of linear Ub chains, resulting in local recruitment of NEMO, activation of IKKα/IKKβ and ultimately NF-κB, which in turn promotes secretion of pro-inflammatory cytokines and restricts bacterial proliferation. Our results establish a role for the linear Ub coat around cytosolic S. Typhimurium as the local NF-κB signalling platform and provide insights into the function of OTULIN in NF-κB activation during bacterial pathogenesis. |
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| Item Description: | Gesehen am 08.10.2018 Im Titel ist Salmonella kursiv dargestellt Im Titel ist Kappa als griechischer Buchstabe dargestellt |
| Physical Description: | Online Resource |
| ISSN: | 2058-5276 |
| DOI: | 10.1038/nmicrobiol.2017.66 |