Watson, Jayne L., Sanchez-Garrido, Julia, Goddard, Philippa J., Torraca, V., Mostowy, Serge, Shenoy, Avinash R. and Clements, Abigail 2019. Shigella sonnei O-Antigen Inhibits Internalization, Vacuole Escape, and Inflammasome Activation. mBio. 10 (6) e02654-19. https://doi.org/10.1128/mbio.02654-19
| Title | Shigella sonnei O-Antigen Inhibits Internalization, Vacuole Escape, and Inflammasome Activation |
|---|---|
| Type | Journal article |
| Authors | Watson, Jayne L., Sanchez-Garrido, Julia, Goddard, Philippa J., Torraca, V., Mostowy, Serge, Shenoy, Avinash R. and Clements, Abigail |
| Abstract | Two Shigella species, Shigella flexneri and Shigella sonnei, cause approximately 90% of bacterial dysentery worldwide. While S. flexneri is the dominant species in low-income countries, S. sonnei causes the majority of infections in middle- and high-income countries. S. flexneri is a prototypic cytosolic bacterium; once intracellular, it rapidly escapes the phagocytic vacuole and causes pyroptosis of macrophages, which is important for pathogenesis and bacterial spread. In contrast, little is known about the invasion, vacuole escape, and induction of pyroptosis during S. sonnei infection of macrophages. We demonstrate here that S. sonnei causes substantially less pyroptosis in human primary monocyte-derived macrophages and THP1 cells. This is due to reduced bacterial uptake and lower relative vacuole escape, which results in fewer cytosolic S. sonnei and hence reduced activation of caspase-1 inflammasomes. Mechanistically, the O-antigen (O-Ag), which in S. sonnei is contained in both the lipopolysaccharide and the capsule, was responsible for reduced uptake and the type 3 secretion system (T3SS) was required for vacuole escape. Our findings suggest that S. sonnei has adapted to an extracellular lifestyle by incorporating multiple layers of O-Ag onto its surface compared to other Shigella species. |
| Article number | e02654-19 |
| Journal | mBio |
| Journal citation | 10 (6) |
| ISSN | 2150-7511 |
| Year | 2019 |
| Publisher | American Society for Microbiology |
| Publisher's version | License CC BY 4.0 File Access Level Open (open metadata and files) |
| Digital Object Identifier (DOI) | https://doi.org/10.1128/mbio.02654-19 |
| Publication dates | |
| Published | 17 Dec 2019 |