A Pseudomonas aeruginosa TIR effector mediates immune evasion by targeting UBAP1 and TLR adaptors
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...
Ausführliche Beschreibung
Autor*in: |
Imbert, Paul RC [verfasserIn] Louche, Arthur [verfasserIn] Luizet, Jean‐Baptiste [verfasserIn] Grandjean, Teddy [verfasserIn] Bigot, Sarah [verfasserIn] Wood, Thomas E [verfasserIn] Gagné, Stéphanie [verfasserIn] Blanco, Amandine [verfasserIn] Wunderley, Lydia [verfasserIn] Terradot, Laurent [verfasserIn] Woodman, Philip [verfasserIn] Garvis, Steve [verfasserIn] Filloux, Alain [verfasserIn] Guery, Benoit [verfasserIn] Salcedo, Suzana P [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
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2017 |
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Anmerkung: |
© The Authors. Published under the terms of the CC BY 4.0 license 2017 |
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Übergeordnetes Werk: |
Enthalten in: The EMBO Journal - Nature Publishing Group UK, 2023, 36(2017), 13 vom: 08. Mai, Seite 1869-1887 |
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Übergeordnetes Werk: |
volume:36 ; year:2017 ; number:13 ; day:08 ; month:05 ; pages:1869-1887 |
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DOI / URN: |
10.15252/embj.201695343 |
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Katalog-ID: |
SPR05790183X |
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245 | 1 | 0 | |a A Pseudomonas aeruginosa TIR effector mediates immune evasion by targeting UBAP1 and TLR adaptors |
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520 | |a 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. | ||
520 | |a Synopsis PumA is a TIR domain‐containing protein required for virulence of the multidrug resistant Pseudomonas aeruginosa PA7 strain. PumA interacts with TLR adaptors but also UBAP1, targeting ESCRT‐I to simultaneously inhibit TLR and TNFR1 signalling. PumA is a virulence factor of multidrug resistant Pseudomonas aeruginosa PA7 strain.PumA mediates inhibition of NFkB and TNFR1 signalling during infection in vitro.The TIR domain of PumA enables interaction with the TLR adaptor TIRAP but most remarkably with the ESCRT‐I component UBAP1.UBAP1 also associates with MyD88 and can impact intracellular sorting of this adaptor. | ||
520 | |a Graphical Abstract PumA from a multi‐drug resistant bacterial strain subverts the host innate immune system through interference with NF‐κB activation by both Toll‐like receptors and inflammatory cytokine receptors. | ||
650 | 4 | |a TIR domain |7 (dpeaa)DE-He213 | |
650 | 4 | |a TLR adaptors |7 (dpeaa)DE-He213 | |
650 | 4 | |a UBAP1 |7 (dpeaa)DE-He213 | |
650 | 4 | |a virulence |7 (dpeaa)DE-He213 | |
700 | 1 | |a Louche, Arthur |e verfasserin |4 aut | |
700 | 1 | |a Luizet, Jean‐Baptiste |e verfasserin |4 aut | |
700 | 1 | |a Grandjean, Teddy |e verfasserin |4 aut | |
700 | 1 | |a Bigot, Sarah |e verfasserin |4 aut | |
700 | 1 | |a Wood, Thomas E |e verfasserin |4 aut | |
700 | 1 | |a Gagné, Stéphanie |e verfasserin |4 aut | |
700 | 1 | |a Blanco, Amandine |e verfasserin |4 aut | |
700 | 1 | |a Wunderley, Lydia |e verfasserin |4 aut | |
700 | 1 | |a Terradot, Laurent |e verfasserin |4 aut | |
700 | 1 | |a Woodman, Philip |e verfasserin |4 aut | |
700 | 1 | |a Garvis, Steve |e verfasserin |4 aut | |
700 | 1 | |a Filloux, Alain |e verfasserin |0 (orcid)0000-0003-1307-0289 |4 aut | |
700 | 1 | |a Guery, Benoit |e verfasserin |4 aut | |
700 | 1 | |a Salcedo, Suzana P |e verfasserin |0 (orcid)0000-0001-5149-7756 |4 aut | |
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10.15252/embj.201695343 doi (DE-627)SPR05790183X (SPR)embj.201695343-e DE-627 ger DE-627 rakwb eng Imbert, Paul RC verfasserin aut A Pseudomonas aeruginosa TIR effector mediates immune evasion by targeting UBAP1 and TLR adaptors 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Authors. Published under the terms of the CC BY 4.0 license 2017 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. Synopsis PumA is a TIR domain‐containing protein required for virulence of the multidrug resistant Pseudomonas aeruginosa PA7 strain. PumA interacts with TLR adaptors but also UBAP1, targeting ESCRT‐I to simultaneously inhibit TLR and TNFR1 signalling. PumA is a virulence factor of multidrug resistant Pseudomonas aeruginosa PA7 strain.PumA mediates inhibition of NFkB and TNFR1 signalling during infection in vitro.The TIR domain of PumA enables interaction with the TLR adaptor TIRAP but most remarkably with the ESCRT‐I component UBAP1.UBAP1 also associates with MyD88 and can impact intracellular sorting of this adaptor. Graphical Abstract PumA from a multi‐drug resistant bacterial strain subverts the host innate immune system through interference with NF‐κB activation by both Toll‐like receptors and inflammatory cytokine receptors. TIR domain (dpeaa)DE-He213 TLR adaptors (dpeaa)DE-He213 UBAP1 (dpeaa)DE-He213 virulence (dpeaa)DE-He213 Louche, Arthur verfasserin aut Luizet, Jean‐Baptiste verfasserin aut Grandjean, Teddy verfasserin aut Bigot, Sarah verfasserin aut Wood, Thomas E verfasserin aut Gagné, Stéphanie verfasserin aut Blanco, Amandine verfasserin aut Wunderley, Lydia verfasserin aut Terradot, Laurent verfasserin aut Woodman, Philip verfasserin aut Garvis, Steve verfasserin aut Filloux, Alain verfasserin (orcid)0000-0003-1307-0289 aut Guery, Benoit verfasserin aut Salcedo, Suzana P verfasserin (orcid)0000-0001-5149-7756 aut Enthalten in The EMBO Journal Nature Publishing Group UK, 2023 36(2017), 13 vom: 08. Mai, Seite 1869-1887 (DE-627)266022529 (DE-600)1467419-1 1460-2075 nnns volume:36 year:2017 number:13 day:08 month:05 pages:1869-1887 https://dx.doi.org/10.15252/embj.201695343 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_211 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 36 2017 13 08 05 1869-1887 |
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10.15252/embj.201695343 doi (DE-627)SPR05790183X (SPR)embj.201695343-e DE-627 ger DE-627 rakwb eng Imbert, Paul RC verfasserin aut A Pseudomonas aeruginosa TIR effector mediates immune evasion by targeting UBAP1 and TLR adaptors 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Authors. Published under the terms of the CC BY 4.0 license 2017 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. Synopsis PumA is a TIR domain‐containing protein required for virulence of the multidrug resistant Pseudomonas aeruginosa PA7 strain. PumA interacts with TLR adaptors but also UBAP1, targeting ESCRT‐I to simultaneously inhibit TLR and TNFR1 signalling. PumA is a virulence factor of multidrug resistant Pseudomonas aeruginosa PA7 strain.PumA mediates inhibition of NFkB and TNFR1 signalling during infection in vitro.The TIR domain of PumA enables interaction with the TLR adaptor TIRAP but most remarkably with the ESCRT‐I component UBAP1.UBAP1 also associates with MyD88 and can impact intracellular sorting of this adaptor. Graphical Abstract PumA from a multi‐drug resistant bacterial strain subverts the host innate immune system through interference with NF‐κB activation by both Toll‐like receptors and inflammatory cytokine receptors. TIR domain (dpeaa)DE-He213 TLR adaptors (dpeaa)DE-He213 UBAP1 (dpeaa)DE-He213 virulence (dpeaa)DE-He213 Louche, Arthur verfasserin aut Luizet, Jean‐Baptiste verfasserin aut Grandjean, Teddy verfasserin aut Bigot, Sarah verfasserin aut Wood, Thomas E verfasserin aut Gagné, Stéphanie verfasserin aut Blanco, Amandine verfasserin aut Wunderley, Lydia verfasserin aut Terradot, Laurent verfasserin aut Woodman, Philip verfasserin aut Garvis, Steve verfasserin aut Filloux, Alain verfasserin (orcid)0000-0003-1307-0289 aut Guery, Benoit verfasserin aut Salcedo, Suzana P verfasserin (orcid)0000-0001-5149-7756 aut Enthalten in The EMBO Journal Nature Publishing Group UK, 2023 36(2017), 13 vom: 08. Mai, Seite 1869-1887 (DE-627)266022529 (DE-600)1467419-1 1460-2075 nnns volume:36 year:2017 number:13 day:08 month:05 pages:1869-1887 https://dx.doi.org/10.15252/embj.201695343 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_211 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 36 2017 13 08 05 1869-1887 |
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10.15252/embj.201695343 doi (DE-627)SPR05790183X (SPR)embj.201695343-e DE-627 ger DE-627 rakwb eng Imbert, Paul RC verfasserin aut A Pseudomonas aeruginosa TIR effector mediates immune evasion by targeting UBAP1 and TLR adaptors 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Authors. Published under the terms of the CC BY 4.0 license 2017 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. Synopsis PumA is a TIR domain‐containing protein required for virulence of the multidrug resistant Pseudomonas aeruginosa PA7 strain. PumA interacts with TLR adaptors but also UBAP1, targeting ESCRT‐I to simultaneously inhibit TLR and TNFR1 signalling. PumA is a virulence factor of multidrug resistant Pseudomonas aeruginosa PA7 strain.PumA mediates inhibition of NFkB and TNFR1 signalling during infection in vitro.The TIR domain of PumA enables interaction with the TLR adaptor TIRAP but most remarkably with the ESCRT‐I component UBAP1.UBAP1 also associates with MyD88 and can impact intracellular sorting of this adaptor. Graphical Abstract PumA from a multi‐drug resistant bacterial strain subverts the host innate immune system through interference with NF‐κB activation by both Toll‐like receptors and inflammatory cytokine receptors. TIR domain (dpeaa)DE-He213 TLR adaptors (dpeaa)DE-He213 UBAP1 (dpeaa)DE-He213 virulence (dpeaa)DE-He213 Louche, Arthur verfasserin aut Luizet, Jean‐Baptiste verfasserin aut Grandjean, Teddy verfasserin aut Bigot, Sarah verfasserin aut Wood, Thomas E verfasserin aut Gagné, Stéphanie verfasserin aut Blanco, Amandine verfasserin aut Wunderley, Lydia verfasserin aut Terradot, Laurent verfasserin aut Woodman, Philip verfasserin aut Garvis, Steve verfasserin aut Filloux, Alain verfasserin (orcid)0000-0003-1307-0289 aut Guery, Benoit verfasserin aut Salcedo, Suzana P verfasserin (orcid)0000-0001-5149-7756 aut Enthalten in The EMBO Journal Nature Publishing Group UK, 2023 36(2017), 13 vom: 08. Mai, Seite 1869-1887 (DE-627)266022529 (DE-600)1467419-1 1460-2075 nnns volume:36 year:2017 number:13 day:08 month:05 pages:1869-1887 https://dx.doi.org/10.15252/embj.201695343 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_211 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 36 2017 13 08 05 1869-1887 |
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10.15252/embj.201695343 doi (DE-627)SPR05790183X (SPR)embj.201695343-e DE-627 ger DE-627 rakwb eng Imbert, Paul RC verfasserin aut A Pseudomonas aeruginosa TIR effector mediates immune evasion by targeting UBAP1 and TLR adaptors 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Authors. Published under the terms of the CC BY 4.0 license 2017 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. Synopsis PumA is a TIR domain‐containing protein required for virulence of the multidrug resistant Pseudomonas aeruginosa PA7 strain. PumA interacts with TLR adaptors but also UBAP1, targeting ESCRT‐I to simultaneously inhibit TLR and TNFR1 signalling. PumA is a virulence factor of multidrug resistant Pseudomonas aeruginosa PA7 strain.PumA mediates inhibition of NFkB and TNFR1 signalling during infection in vitro.The TIR domain of PumA enables interaction with the TLR adaptor TIRAP but most remarkably with the ESCRT‐I component UBAP1.UBAP1 also associates with MyD88 and can impact intracellular sorting of this adaptor. Graphical Abstract PumA from a multi‐drug resistant bacterial strain subverts the host innate immune system through interference with NF‐κB activation by both Toll‐like receptors and inflammatory cytokine receptors. TIR domain (dpeaa)DE-He213 TLR adaptors (dpeaa)DE-He213 UBAP1 (dpeaa)DE-He213 virulence (dpeaa)DE-He213 Louche, Arthur verfasserin aut Luizet, Jean‐Baptiste verfasserin aut Grandjean, Teddy verfasserin aut Bigot, Sarah verfasserin aut Wood, Thomas E verfasserin aut Gagné, Stéphanie verfasserin aut Blanco, Amandine verfasserin aut Wunderley, Lydia verfasserin aut Terradot, Laurent verfasserin aut Woodman, Philip verfasserin aut Garvis, Steve verfasserin aut Filloux, Alain verfasserin (orcid)0000-0003-1307-0289 aut Guery, Benoit verfasserin aut Salcedo, Suzana P verfasserin (orcid)0000-0001-5149-7756 aut Enthalten in The EMBO Journal Nature Publishing Group UK, 2023 36(2017), 13 vom: 08. Mai, Seite 1869-1887 (DE-627)266022529 (DE-600)1467419-1 1460-2075 nnns volume:36 year:2017 number:13 day:08 month:05 pages:1869-1887 https://dx.doi.org/10.15252/embj.201695343 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_211 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 36 2017 13 08 05 1869-1887 |
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10.15252/embj.201695343 doi (DE-627)SPR05790183X (SPR)embj.201695343-e DE-627 ger DE-627 rakwb eng Imbert, Paul RC verfasserin aut A Pseudomonas aeruginosa TIR effector mediates immune evasion by targeting UBAP1 and TLR adaptors 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Authors. Published under the terms of the CC BY 4.0 license 2017 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. Synopsis PumA is a TIR domain‐containing protein required for virulence of the multidrug resistant Pseudomonas aeruginosa PA7 strain. PumA interacts with TLR adaptors but also UBAP1, targeting ESCRT‐I to simultaneously inhibit TLR and TNFR1 signalling. PumA is a virulence factor of multidrug resistant Pseudomonas aeruginosa PA7 strain.PumA mediates inhibition of NFkB and TNFR1 signalling during infection in vitro.The TIR domain of PumA enables interaction with the TLR adaptor TIRAP but most remarkably with the ESCRT‐I component UBAP1.UBAP1 also associates with MyD88 and can impact intracellular sorting of this adaptor. Graphical Abstract PumA from a multi‐drug resistant bacterial strain subverts the host innate immune system through interference with NF‐κB activation by both Toll‐like receptors and inflammatory cytokine receptors. TIR domain (dpeaa)DE-He213 TLR adaptors (dpeaa)DE-He213 UBAP1 (dpeaa)DE-He213 virulence (dpeaa)DE-He213 Louche, Arthur verfasserin aut Luizet, Jean‐Baptiste verfasserin aut Grandjean, Teddy verfasserin aut Bigot, Sarah verfasserin aut Wood, Thomas E verfasserin aut Gagné, Stéphanie verfasserin aut Blanco, Amandine verfasserin aut Wunderley, Lydia verfasserin aut Terradot, Laurent verfasserin aut Woodman, Philip verfasserin aut Garvis, Steve verfasserin aut Filloux, Alain verfasserin (orcid)0000-0003-1307-0289 aut Guery, Benoit verfasserin aut Salcedo, Suzana P verfasserin (orcid)0000-0001-5149-7756 aut Enthalten in The EMBO Journal Nature Publishing Group UK, 2023 36(2017), 13 vom: 08. Mai, Seite 1869-1887 (DE-627)266022529 (DE-600)1467419-1 1460-2075 nnns volume:36 year:2017 number:13 day:08 month:05 pages:1869-1887 https://dx.doi.org/10.15252/embj.201695343 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_211 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 36 2017 13 08 05 1869-1887 |
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Enthalten in The EMBO Journal 36(2017), 13 vom: 08. Mai, Seite 1869-1887 volume:36 year:2017 number:13 day:08 month:05 pages:1869-1887 |
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Imbert, Paul RC @@aut@@ Louche, Arthur @@aut@@ Luizet, Jean‐Baptiste @@aut@@ Grandjean, Teddy @@aut@@ Bigot, Sarah @@aut@@ Wood, Thomas E @@aut@@ Gagné, Stéphanie @@aut@@ Blanco, Amandine @@aut@@ Wunderley, Lydia @@aut@@ Terradot, Laurent @@aut@@ Woodman, Philip @@aut@@ Garvis, Steve @@aut@@ Filloux, Alain @@aut@@ Guery, Benoit @@aut@@ Salcedo, Suzana P @@aut@@ |
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<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000naa a22002652 4500</leader><controlfield tag="001">SPR05790183X</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20241019064919.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">241019s2017 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.15252/embj.201695343</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR05790183X</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)embj.201695343-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Imbert, Paul RC</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">A Pseudomonas aeruginosa TIR effector mediates immune evasion by targeting UBAP1 and TLR adaptors</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2017</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="500" ind1=" " ind2=" "><subfield code="a">© The Authors. Published under the terms of the CC BY 4.0 license 2017</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">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.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Synopsis PumA is a TIR domain‐containing protein required for virulence of the multidrug resistant Pseudomonas aeruginosa PA7 strain. PumA interacts with TLR adaptors but also UBAP1, targeting ESCRT‐I to simultaneously inhibit TLR and TNFR1 signalling. PumA is a virulence factor of multidrug resistant Pseudomonas aeruginosa PA7 strain.PumA mediates inhibition of NFkB and TNFR1 signalling during infection in vitro.The TIR domain of PumA enables interaction with the TLR adaptor TIRAP but most remarkably with the ESCRT‐I component UBAP1.UBAP1 also associates with MyD88 and can impact intracellular sorting of this adaptor.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Graphical Abstract PumA from a multi‐drug resistant bacterial strain subverts the host innate immune system through interference with NF‐κB activation by both Toll‐like receptors and inflammatory cytokine receptors.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">TIR domain</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">TLR adaptors</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">UBAP1</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">virulence</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Louche, Arthur</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Luizet, Jean‐Baptiste</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Grandjean, Teddy</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Bigot, Sarah</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Wood, Thomas E</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Gagné, Stéphanie</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Blanco, Amandine</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Wunderley, Lydia</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Terradot, Laurent</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Woodman, Philip</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Garvis, Steve</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Filloux, Alain</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(orcid)0000-0003-1307-0289</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Guery, Benoit</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Salcedo, Suzana P</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(orcid)0000-0001-5149-7756</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">The EMBO Journal</subfield><subfield code="d">Nature Publishing Group UK, 2023</subfield><subfield code="g">36(2017), 13 vom: 08. 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author |
Imbert, Paul RC |
spellingShingle |
Imbert, Paul RC misc TIR domain misc TLR adaptors misc UBAP1 misc virulence A Pseudomonas aeruginosa TIR effector mediates immune evasion by targeting UBAP1 and TLR adaptors |
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Imbert, Paul RC |
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1460-2075 |
topic_title |
A Pseudomonas aeruginosa TIR effector mediates immune evasion by targeting UBAP1 and TLR adaptors TIR domain (dpeaa)DE-He213 TLR adaptors (dpeaa)DE-He213 UBAP1 (dpeaa)DE-He213 virulence (dpeaa)DE-He213 |
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misc TIR domain misc TLR adaptors misc UBAP1 misc virulence |
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misc TIR domain misc TLR adaptors misc UBAP1 misc virulence |
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misc TIR domain misc TLR adaptors misc UBAP1 misc virulence |
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Elektronische Aufsätze Aufsätze Elektronische Ressource |
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title |
A Pseudomonas aeruginosa TIR effector mediates immune evasion by targeting UBAP1 and TLR adaptors |
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(DE-627)SPR05790183X (SPR)embj.201695343-e |
title_full |
A Pseudomonas aeruginosa TIR effector mediates immune evasion by targeting UBAP1 and TLR adaptors |
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Imbert, Paul RC |
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Imbert, Paul RC Louche, Arthur Luizet, Jean‐Baptiste 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 |
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a pseudomonas aeruginosa tir effector mediates immune evasion by targeting ubap1 and tlr adaptors |
title_auth |
A Pseudomonas aeruginosa TIR effector mediates immune evasion by targeting UBAP1 and TLR adaptors |
abstract |
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. Synopsis PumA is a TIR domain‐containing protein required for virulence of the multidrug resistant Pseudomonas aeruginosa PA7 strain. PumA interacts with TLR adaptors but also UBAP1, targeting ESCRT‐I to simultaneously inhibit TLR and TNFR1 signalling. PumA is a virulence factor of multidrug resistant Pseudomonas aeruginosa PA7 strain.PumA mediates inhibition of NFkB and TNFR1 signalling during infection in vitro.The TIR domain of PumA enables interaction with the TLR adaptor TIRAP but most remarkably with the ESCRT‐I component UBAP1.UBAP1 also associates with MyD88 and can impact intracellular sorting of this adaptor. Graphical Abstract PumA from a multi‐drug resistant bacterial strain subverts the host innate immune system through interference with NF‐κB activation by both Toll‐like receptors and inflammatory cytokine receptors. © The Authors. Published under the terms of the CC BY 4.0 license 2017 |
abstractGer |
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. Synopsis PumA is a TIR domain‐containing protein required for virulence of the multidrug resistant Pseudomonas aeruginosa PA7 strain. PumA interacts with TLR adaptors but also UBAP1, targeting ESCRT‐I to simultaneously inhibit TLR and TNFR1 signalling. PumA is a virulence factor of multidrug resistant Pseudomonas aeruginosa PA7 strain.PumA mediates inhibition of NFkB and TNFR1 signalling during infection in vitro.The TIR domain of PumA enables interaction with the TLR adaptor TIRAP but most remarkably with the ESCRT‐I component UBAP1.UBAP1 also associates with MyD88 and can impact intracellular sorting of this adaptor. Graphical Abstract PumA from a multi‐drug resistant bacterial strain subverts the host innate immune system through interference with NF‐κB activation by both Toll‐like receptors and inflammatory cytokine receptors. © The Authors. Published under the terms of the CC BY 4.0 license 2017 |
abstract_unstemmed |
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. Synopsis PumA is a TIR domain‐containing protein required for virulence of the multidrug resistant Pseudomonas aeruginosa PA7 strain. PumA interacts with TLR adaptors but also UBAP1, targeting ESCRT‐I to simultaneously inhibit TLR and TNFR1 signalling. PumA is a virulence factor of multidrug resistant Pseudomonas aeruginosa PA7 strain.PumA mediates inhibition of NFkB and TNFR1 signalling during infection in vitro.The TIR domain of PumA enables interaction with the TLR adaptor TIRAP but most remarkably with the ESCRT‐I component UBAP1.UBAP1 also associates with MyD88 and can impact intracellular sorting of this adaptor. Graphical Abstract PumA from a multi‐drug resistant bacterial strain subverts the host innate immune system through interference with NF‐κB activation by both Toll‐like receptors and inflammatory cytokine receptors. © The Authors. Published under the terms of the CC BY 4.0 license 2017 |
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A Pseudomonas aeruginosa TIR effector mediates immune evasion by targeting UBAP1 and TLR adaptors |
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Louche, Arthur Luizet, Jean‐Baptiste 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 |
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|
score |
7.401127 |