| Autor: |
Aurélien Boyance, Karin Santoni, Stephen Adonai Leon-Icaza, Hans Clevers, Yoann Rombouts, Arnaud Métais, Etienne Meunier, Agnès Coste, Emmanuelle Naser, Ina Attrée, Peter J. Peters, Rémi Planès, Audrey Hessel, Elif Eren, Salimata Bagayoko, Céline Berrone, Céline Cougoule, N. Iacobachvili, Pierre-Jean Bordignon, Miriam Pinilla, Flavie Moreau, Lise Lefèvre, Dara W. Frank |
| Rok vydání: |
2021 |
| Předmět: |
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| DOI: |
10.1101/2021.02.17.431580 |
| Popis: |
SummaryRegulated cell necrosis supports immune and anti-infectious strategies of the body; however, dysregulation of these processes drives pathological organ damage.Pseudomonas aeruginosaexpresses a phospholipase, ExoU that triggers pathological host cell necrosis through a poorly characterized pathway. Here, we investigated the molecular and cellular mechanisms of ExoU-mediated necrosis. We show that cellular peroxidised phospholipids enhance ExoU phospholipase activity, which drives necrosis of immune and non-immune cells. Conversely, both the endogenous lipid peroxidation regulator GPX4 and the pharmacological inhibition of lipid peroxidation delay ExoU-dependent cell necrosis and improve bacterial eliminationin vitroandin vivo. Our findings also pertain to the ExoU-related phospholipase from the bacterial pathogenBurkholderia thailandensis, suggesting that exploitation of peroxidised phospholipids might be a conserved virulence mechanism among various microbial phospholipases. Overall, our results identify an original lipid peroxidation-based virulence mechanism as a strong contributor of microbial phospholipase-driven pathology. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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