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Peptidoglycan editi...
Peptidoglycan editing in non-proliferating intracellular Salmonella as source of interference with immune signaling
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- Hernández, Sara B. (författare)
- Umeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Umeå Centre for Microbial Research (UCMR),Institutionen för molekylärbiologi (Medicinska fakulteten)
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- Castanheira, Sónia (författare)
- Laboratory of Intracellular Bacterial Pathogens, National Centre for Biotechnology (CNB)-CSIC, Madrid, Spain
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- Graciela Pucciarelli, M. (författare)
- Laboratory of Intracellular Bacterial Pathogens, National Centre for Biotechnology (CNB)-CSIC, Madrid, Spain; Department of Molecular Biology, Universidad Autónoma de Madrid (UAM), Madrid, Spain; Center for Molecular Biology “Severo Ochoa” (CBMSO)-CSIC, Madrid, Spain
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- Cestero, Juan J. (författare)
- Laboratory of Intracellular Bacterial Pathogens, National Centre for Biotechnology (CNB)-CSIC, Madrid, Spain
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- Rico-Pérez, Gadea (författare)
- Laboratory of Intracellular Bacterial Pathogens, National Centre for Biotechnology (CNB)-CSIC, Madrid, Spain
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- Paradela, Alberto (författare)
- Proteomics Unit, National Centre for Biotechnology (CNB)-CSIC, Madrid, Spain
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- Ayala, Juan A. (författare)
- Center for Molecular Biology “Severo Ochoa” (CBMSO)-CSIC, Madrid, Spain
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- Velázquez, Sonsoles (författare)
- Institute of Medicinal Chemistry (IQM)-CSIC, Madrid, Spain
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- San-Félix, Ana (författare)
- Institute of Medicinal Chemistry (IQM)-CSIC, Madrid, Spain
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- Cava, Felipe (författare)
- Umeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Umeå Centre for Microbial Research (UCMR),Institutionen för molekylärbiologi (Medicinska fakulteten)
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- Portillo, Francisco García-Del (författare)
- Laboratory of Intracellular Bacterial Pathogens, National Centre for Biotechnology (CNB)-CSIC, Madrid, Spain
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(creator_code:org_t)
- 2022-01-25
- 2022
- Engelska.
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Ingår i: PLoS Pathogens. - : Public Library of Science. - 1553-7366 .- 1553-7374. ; 18:1
- Relaterad länk:
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https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
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https://journals.plo...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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-cross-link, a type of bridge shared by all the atypical crosslinked muropeptides identified. The L,Dtranspeptidases 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
- NATURVETENSKAP -- Biologi -- Mikrobiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Microbiology (hsv//eng)
Nyckelord
- mikrobiologi
- Microbiology
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Hernández, Sara ...
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Castanheira, Són ...
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Graciela Pucciar ...
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Cestero, Juan J.
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Rico-Pérez, Gade ...
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Paradela, Albert ...
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Ayala, Juan A.
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Velázquez, Sonso ...
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San-Félix, Ana
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Cava, Felipe
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Portillo, Franci ...
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