A Pseudomonas aeruginosa TIR effector mediates immune evasion by targeting UBAP1 and TLR adaptors |
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| Authors: | Paul RC Imbert Arthur Louche Jean‐Baptiste Luizet Teddy Grandjean Sarah Bigot Thomas E Wood Stéphanie Gagné Amandine Blanco Lydia Wunderley Laurent Terradot Philip Woodman Steve Garvis Alain Filloux Benoit Guery Suzana P Salcedo |
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| Affiliation: | 1. Laboratory of Molecular Microbiology and Structural Biochemistry, Centre National de la Recherche Scientifique, University of Lyon, Lyon, France;2. EA 7366 Recherche Translationelle Relations H?te‐Pathogènes, Faculté de Médecine P?le Recherche, Université Lille 2, Lille, France;3. MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, UK;4. School of Biological Sciences, Faculty of Biology Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK?;5. Laboratoire de Biologie et Modelisation, Ecole Normal Supérieur, UMR5239, Lyon, France |
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| Abstract: | Bacterial pathogens often subvert the innate immune system to establish a successful infection. The direct inhibition of downstream components of innate immune pathways is particularly well documented but how bacteria interfere with receptor proximal events is far less well understood. Here, we describe a Toll/interleukin 1 receptor (TIR) domain‐containing protein (PumA) of the multi‐drug resistant Pseudomonas aeruginosa PA7 strain. We found that PumA is essential for virulence and inhibits NF‐κB, a property transferable to non‐PumA strain PA14, suggesting no additional factors are needed for PumA function. The TIR domain is able to interact with the Toll‐like receptor (TLR) adaptors TIRAP and MyD88, as well as the ubiquitin‐associated protein 1 (UBAP1), a component of the endosomal‐sorting complex required for transport I (ESCRT‐I). These interactions are not spatially exclusive as we show UBAP1 can associate with MyD88, enhancing its plasma membrane localization. Combined targeting of UBAP1 and TLR adaptors by PumA impedes both cytokine and TLR receptor signalling, highlighting a novel strategy for innate immune evasion. |
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| Keywords: |
Pseudomonas
TIR domain TLR adaptors UBAP1 virulence |
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