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PMID:22901537
Citation |
Liu, M, Haenssler, E, Uehara, T, Losick, VP, Park, JT and Isberg, RR (2012) The Legionella pneumophila EnhC protein interferes with immunostimulatory muramyl peptide production to evade innate immunity. Cell Host Microbe 12:166-76 |
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Abstract |
Successful pathogens have evolved to evade innate immune recognition of microbial molecules by pattern recognition receptors (PRR), which control microbial growth in host tissues. Upon Legionella pneumophila infection of macrophages, the cytosolic PRR Nod1 recognizes anhydro-disaccharide-tetrapeptide (anhDSTP) generated by soluble lytic transglycosylase (SltL), the predominant bacterial peptidoglycan degrading enzyme, to activate NF-κB-dependent innate immune responses. We show that L. pneumophila periplasmic protein EnhC, which is uniquely required for bacterial replication within macrophages, interferes with SltL to lower anhDSTP production. L. pneumophila mutant strains lacking EnhC (ΔenhC) increase Nod1-dependent NF-κB activation in host cells, while reducing SltL activity in a ΔenhC strain restores intracellular bacterial growth. Further, L. pneumophila ΔenhC is specifically rescued in Nod1- but not Nod2-deficient macrophages, arguing that EnhC facilitates evasion from Nod1 recognition. These results indicate that a bacterial pathogen regulates peptidoglycan degradation to control the production of PRR ligands and evade innate immune recognition. |
Links |
PubMed PMC3678716 Online version:10.1016/j.chom.2012.06.004 |
Keywords |
Bacterial Proteins/genetics; Bacterial Proteins/immunology; Bacterial Proteins/metabolism; Glycosyltransferases/genetics; Glycosyltransferases/immunology; Immune Evasion; Immunity, Innate; Legionella pneumophila/enzymology; Legionella pneumophila/genetics; Legionella pneumophila/immunology; Legionnaires' Disease/genetics; Legionnaires' Disease/immunology; Legionnaires' Disease/microbiology; Macrophages/immunology; Macrophages/microbiology; NF-kappa B/genetics; NF-kappa B/immunology; Nod1 Signaling Adaptor Protein/genetics; Nod1 Signaling Adaptor Protein/immunology; Peptides/immunology |
Significance
Annotations
Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
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Contributes to |
GO:0003674: molecular function |
ECO:0000315: |
F |
Figure 3 shows that EnhC binds to murein transglycosylase (sltL), which degrades peptidoglycan, and inhibits it, causing L. pneumophila to be able to survive in macrophages |
complete | |||
Notes
See also
References
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