A Pseudomonas aeruginosa TIR effector mediates immune evasion by targeting UBAP1 and TLR adaptors

• Paul RC Imbert ^[1] ; Arthur Louche ^[1] ; Jean‐Baptiste Luizet ^[1] ; Teddy Grandjean ^[4] ; Sarah Bigot ^[1] ; Thomas E Wood ^[2] ; Stéphanie Gagné ^[1] ; Amandine Blanco ^[1] ; Lydia Wunderley ^[3] ; Laurent Terradot ^[1] ; Philip Woodman ^[3] ; Steve Garvis ^[5] ; Alain Filloux ^[2] ; Benoit Guery ^[4] ; Suzana P Salcedo ^[1]
  1. [1] University of Lyon System

     University of Lyon System

     Arrondissement de Lyon, Francia

     
  2. [2] Imperial College London

     Imperial College London

     Reino Unido

     
  3. [3] University of Manchester

     University of Manchester

     Reino Unido

     
  4. [4] 2 EA 7366 Recherche Translationelle Relations Hôte‐Pathogènes Faculté de Médecine Pôle Recherche Université Lille 2 Lille France
  5. [5] 5 Laboratoire de Biologie et Modelisation Ecole Normal Supérieur UMR5239 Lyon France

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• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 36, Nº. 13, 2017, págs. 1869-1887
• Idioma: inglés
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  • 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.