Evasion of autophagy mediated by Rickettsia surface protein OmpB is critical for virulence
| Autor: | Matthew D. Welch, Patrik Engström, Michael Rape, Kevin G. Mark, Nadia Ingabire, Anthony T. Iavarone, Guillaume Golovkine, Gabriel Mitchell, Thomas P. Burke, Jeffery S. Cox |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Applied Microbiology and Biotechnology
Gene Knockout Techniques Mice Cytosol Ubiquitin Chlorocebus aethiops Rickettsia Polyubiquitin innate immunity autophagic recognition 0303 health sciences Host cell cytosol Virulence biology OmpB OmpA Cell biology polyubiquitylation intracellular pathogens Female Bacterial outer membrane Microtubule-Associated Proteins Bacterial Outer Membrane Proteins Microbiology (medical) Immunology Microbiology Article Cell Line 03 medical and health sciences Immune system Autophagy Genetics Animals Humans antimicrobial autophagy Vero Cells Immune Evasion 030304 developmental biology 030306 microbiology Macrophages Intracellular parasite Endothelial Cells Rickettsia Infections Cell Biology biology.organism_classification Mice Inbred C57BL Disease Models Animal A549 Cells biology.protein Transcriptome |
| Zdroj: | Nature microbiology |
| ISSN: | 2058-5276 |
| Popis: | Rickettsia are obligate intracellular bacteria that evade antimicrobial autophagy in the host cell cytosol by unknown mechanisms. Other cytosolic pathogens block different steps of autophagy targeting, including the initial step of polyubiquitin-coat formation. One mechanism of evasion is to mobilize actin to the bacterial surface. Here, we show that actin mobilization is insufficient to block autophagy recognition of the pathogen Rickettsia parkeri. Instead, R. parkeri employs outer membrane protein B (OmpB) to block ubiquitylation of the bacterial surface proteins, including OmpA, and subsequent recognition by autophagy receptors. OmpB is also required for the formation of a capsule-like layer. Although OmpB is dispensable for bacterial growth in endothelial cells, it is essential for R. parkeri to block autophagy in macrophages and to colonize mice because of its ability to promote autophagy evasion in immune cells. Our results indicate that OmpB acts as a protective shield to obstruct autophagy recognition, thereby revealing a distinctive bacterial mechanism to evade antimicrobial autophagy. |
| Databáze: | OpenAIRE |
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