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

Paul R.C. 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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article numbere201695343
Pages (from-to)1299-1464
Number of pages66
JournalEMBO Journal
Volume36
Issue number10
Early online date8 May 2017
DOIs
Publication statusPublished - 15 May 2017

Keywords

  • Pseudomonas
  • TIR domain
  • TLR adaptors
  • UBAP1
  • Virulence

Fingerprint

Dive into the research topics of 'A Pseudomonas aeruginosa TIR effector mediates immune evasion by targeting UBAP1 and TLR adaptors'. Together they form a unique fingerprint.

Cite this