| Mutations of the Listeria monocytogenes peptidoglycan N-deacetylase and O-acetylase result in enhanced lysozyme sensitivity, bacteriolysis, and hyperinduction of innate immune pathways. | |
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MedLine Citation:
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PMID: 21768286 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Listeria monocytogenes is a Gram-positive intracellular pathogen that is naturally resistant to lysozyme. Recently, it was shown that peptidoglycan modification by N-deacetylation or O-acetylation confers resistance to lysozyme in various Gram-positive bacteria, including L. monocytogenes. L. monocytogenes peptidoglycan is deacetylated by the action of N-acetylglucosamine deacetylase (Pgd) and acetylated by O-acetylmuramic acid transferase (Oat). We characterized Pgd(-), Oat(-), and double mutants to determine the specific role of L. monocytogenes peptidoglycan acetylation in conferring lysozyme sensitivity during infection of macrophages and mice. Pgd(-) and Pgd(-) Oat(-) double mutants were attenuated approximately 2 and 3.5 logs, respectively, in vivo. In bone-marrow derived macrophages, the mutants demonstrated intracellular growth defects and increased induction of cytokine transcriptional responses that emanated from a phagosome and the cytosol. Lysozyme-sensitive mutants underwent bacteriolysis in the macrophage cytosol, resulting in AIM2-dependent pyroptosis. Each of the in vitro phenotypes was rescued upon infection of LysM(-) macrophages. The addition of extracellular lysozyme to LysM(-) macrophages restored cytokine induction, host cell death, and L. monocytogenes growth inhibition. This surprising observation suggests that extracellular lysozyme can access the macrophage cytosol and act on intracellular lysozyme-sensitive bacteria. |
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Authors:
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Chris S Rae; Aimee Geissler; Paul C Adamson; Daniel A Portnoy |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2011-07-18 |
Journal Detail:
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Title: Infection and immunity Volume: 79 ISSN: 1098-5522 ISO Abbreviation: Infect. Immun. Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-08-17 Completed Date: 2011-10-21 Revised Date: 2012-03-01 |
Medline Journal Info:
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Nlm Unique ID: 0246127 Medline TA: Infect Immun Country: United States |
Other Details:
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Languages: eng Pagination: 3596-606 Citation Subset: IM |
Affiliation:
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Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720-3202, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acetylation Amidohydrolases / genetics, metabolism* Animals Apoptosis Bacteriolysis Cytokines / biosynthesis Female Immunity, Innate* Listeria monocytogenes / enzymology*, genetics, growth & development, immunology* Macrophages / immunology, metabolism, microbiology Mice Mice, Inbred C57BL Muramidase / metabolism* Mutation Peptidoglycan / immunology, metabolism RNA Interference RNA, Small Interfering Reverse Transcriptase Polymerase Chain Reaction Signal Transduction Transferases / genetics, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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A1063302//PHS HHS; AI27655/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cytokines; 0/Peptidoglycan; 0/RNA, Small Interfering; EC 2.-/Transferases; EC 3.2.1.17/Muramidase; EC 3.5.-/Amidohydrolases; EC 3.5.1.33/N-acetylglucosamine deacetylase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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