Peptidoglycan editing in non-proliferating intracellular Salmonella as source of interference with immune signaling

Salmonella enterica causes intracellular infections that can be limited to the intestine or spread to deeper tissues. In most cases, intracellular bacteria show moderate growth. How these bacteria face host defenses that recognize peptidoglycan, is poorly understood. Here, we report a high-resolutio...

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Autores: Hernández, Sara B., Castanheira, Sónia, Pucciarelli, María Graciela, Cestero, Juan J., Rico Pérez, Gadea, Paradela, Alberto, Ayala, Juan A, Velázquez, Sonsoles, San-Félix, Ana, Cava, Felipe, García del Portillo, Francisco
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/260643
Acceso en línea:http://hdl.handle.net/10261/260643
https://api.elsevier.com/content/abstract/scopus_id/85124039163
Access Level:acceso abierto
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spelling Peptidoglycan editing in non-proliferating intracellular Salmonella as source of interference with immune signalingHernández, Sara B.Castanheira, SóniaPucciarelli, María GracielaCestero, Juan J.Rico Pérez, GadeaParadela, AlbertoAyala, Juan AVelázquez, SonsolesSan-Félix, AnaCava, FelipeGarcía del Portillo, FranciscoSalmonella enterica causes intracellular infections that can be limited to the intestine or spread to deeper tissues. In most cases, intracellular bacteria show moderate growth. How these bacteria face host defenses that recognize peptidoglycan, is poorly understood. Here, we report a high-resolution structural analysis of the minute amounts of peptidoglycan purified from S. enterica serovar Typhimurium (S. Typhimurium) infecting fibroblasts, a cell type in which this pathogen undergoes moderate growth and persists for days intracellularly. The peptidoglycan of these non-proliferating bacteria contains atypical crosslinked muropeptides with stem peptides trimmed at the L-alanine-D-glutamic acid-(γ) or D-glutamic acid-(γ)-meso-diaminopimelic acid motifs, both sensed by intracellular immune receptors. This peptidoglycan has a reduced glycan chain average length and ~30% increase in the L,D-crosslink, a type of bridge shared by all the atypical crosslinked muropeptides identified. The L,D-transpeptidases LdtD (YcbB) and LdtE (YnhG) are responsible for the formation of these L,D-bridges in the peptidoglycan of intracellular bacteria. We also identified in a fraction of muropeptides an unprecedented modification in the peptidoglycan of intracellular S. Typhimurium consisting of the amino alcohol alaninol replacing the terminal (fourth) D-alanine. Alaninol was still detectable in the peptidoglycan of a double mutant lacking LdtD and LdtE, thereby ruling out the contribution of these enzymes to this chemical modification. Remarkably, all multiple mutants tested lacking candidate enzymes that either trim stem peptides or form the L,D-bridges retain the capacity to modify the terminal D-alanine to alaninol and all attenuate NF-κB nuclear translocation. These data inferred a potential role of alaninol-containing muropeptides in attenuating pro-inflammatory signaling, which was confirmed with a synthetic tetrapeptide bearing such amino alcohol. We suggest that the modification of D-alanine to alaninol in the peptidoglycan of non-proliferating intracellular S. Typhimurium is an editing process exploited by this pathogen to evade immune recognition inside host cells.Peer reviewedPucciarelli, María Graciela [0000-0002-4268-2316]San-Félix, Ana [0000-0003-4271-7598]García del Portillo, Francisco [0000-0002-4120-0530]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202220222022info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501http://hdl.handle.net/10261/260643https://api.elsevier.com/content/abstract/scopus_id/85124039163reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)InglésPLoS pathogensSíinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2606432026-05-22T06:33:51Z
dc.title.none.fl_str_mv Peptidoglycan editing in non-proliferating intracellular Salmonella as source of interference with immune signaling
title Peptidoglycan editing in non-proliferating intracellular Salmonella as source of interference with immune signaling
spellingShingle Peptidoglycan editing in non-proliferating intracellular Salmonella as source of interference with immune signaling
Hernández, Sara B.
title_short Peptidoglycan editing in non-proliferating intracellular Salmonella as source of interference with immune signaling
title_full Peptidoglycan editing in non-proliferating intracellular Salmonella as source of interference with immune signaling
title_fullStr Peptidoglycan editing in non-proliferating intracellular Salmonella as source of interference with immune signaling
title_full_unstemmed Peptidoglycan editing in non-proliferating intracellular Salmonella as source of interference with immune signaling
title_sort Peptidoglycan editing in non-proliferating intracellular Salmonella as source of interference with immune signaling
dc.creator.none.fl_str_mv Hernández, Sara B.
Castanheira, Sónia
Pucciarelli, María Graciela
Cestero, Juan J.
Rico Pérez, Gadea
Paradela, Alberto
Ayala, Juan A
Velázquez, Sonsoles
San-Félix, Ana
Cava, Felipe
García del Portillo, Francisco
author Hernández, Sara B.
author_facet Hernández, Sara B.
Castanheira, Sónia
Pucciarelli, María Graciela
Cestero, Juan J.
Rico Pérez, Gadea
Paradela, Alberto
Ayala, Juan A
Velázquez, Sonsoles
San-Félix, Ana
Cava, Felipe
García del Portillo, Francisco
author_role author
author2 Castanheira, Sónia
Pucciarelli, María Graciela
Cestero, Juan J.
Rico Pérez, Gadea
Paradela, Alberto
Ayala, Juan A
Velázquez, Sonsoles
San-Félix, Ana
Cava, Felipe
García del Portillo, Francisco
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Pucciarelli, María Graciela [0000-0002-4268-2316]
San-Félix, Ana [0000-0003-4271-7598]
García del Portillo, Francisco [0000-0002-4120-0530]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
description Salmonella enterica causes intracellular infections that can be limited to the intestine or spread to deeper tissues. In most cases, intracellular bacteria show moderate growth. How these bacteria face host defenses that recognize peptidoglycan, is poorly understood. Here, we report a high-resolution structural analysis of the minute amounts of peptidoglycan purified from S. enterica serovar Typhimurium (S. Typhimurium) infecting fibroblasts, a cell type in which this pathogen undergoes moderate growth and persists for days intracellularly. The peptidoglycan of these non-proliferating bacteria contains atypical crosslinked muropeptides with stem peptides trimmed at the L-alanine-D-glutamic acid-(γ) or D-glutamic acid-(γ)-meso-diaminopimelic acid motifs, both sensed by intracellular immune receptors. This peptidoglycan has a reduced glycan chain average length and ~30% increase in the L,D-crosslink, a type of bridge shared by all the atypical crosslinked muropeptides identified. The L,D-transpeptidases LdtD (YcbB) and LdtE (YnhG) are responsible for the formation of these L,D-bridges in the peptidoglycan of intracellular bacteria. We also identified in a fraction of muropeptides an unprecedented modification in the peptidoglycan of intracellular S. Typhimurium consisting of the amino alcohol alaninol replacing the terminal (fourth) D-alanine. Alaninol was still detectable in the peptidoglycan of a double mutant lacking LdtD and LdtE, thereby ruling out the contribution of these enzymes to this chemical modification. Remarkably, all multiple mutants tested lacking candidate enzymes that either trim stem peptides or form the L,D-bridges retain the capacity to modify the terminal D-alanine to alaninol and all attenuate NF-κB nuclear translocation. These data inferred a potential role of alaninol-containing muropeptides in attenuating pro-inflammatory signaling, which was confirmed with a synthetic tetrapeptide bearing such amino alcohol. We suggest that the modification of D-alanine to alaninol in the peptidoglycan of non-proliferating intracellular S. Typhimurium is an editing process exploited by this pathogen to evade immune recognition inside host cells.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/260643
https://api.elsevier.com/content/abstract/scopus_id/85124039163
url http://hdl.handle.net/10261/260643
https://api.elsevier.com/content/abstract/scopus_id/85124039163
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv PLoS pathogens
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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