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A Pseudomonas aeruginosa TIR effector mediates immune evasion by targeting UBAP 1 and TLR adaptors
Author(s) -
Imbert Paul RC,
Louche Arthur,
Luizet JeanBaptiste,
Grandjean Teddy,
Bigot Sarah,
Wood Thomas E,
Gagné Stéphanie,
Blanco Amandine,
Wunderley Lydia,
Terradot Laurent,
Woodman Philip,
Garvis Steve,
Filloux Alain,
Guery Benoit,
Salcedo Suzana P
Publication year - 2017
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201695343
Subject(s) - biology , innate immune system , puma , immune system , microbiology and biotechnology , toll like receptor , endosome , receptor , effector , immunology , intracellular , gene , biochemistry
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 PA 7 strain. We found that PumA is essential for virulence and inhibits NF ‐κB, a property transferable to non‐PumA strain PA 14, 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 ( UBAP 1), a component of the endosomal‐sorting complex required for transport I ( ESCRT ‐I). These interactions are not spatially exclusive as we show UBAP 1 can associate with MyD88, enhancing its plasma membrane localization. Combined targeting of UBAP 1 and TLR adaptors by PumA impedes both cytokine and TLR receptor signalling, highlighting a novel strategy for innate immune evasion.