Direct bacterial killing in vitro by recombinant Nod2 is compromised by Crohn's disease-associated mutations

Details

Serval ID
serval:BIB_EBDC954A1085
Type
Article: article from journal or magazin.
Collection
Publications
Title
Direct bacterial killing in vitro by recombinant Nod2 is compromised by Crohn's disease-associated mutations
Journal
PLoS One
Author(s)
Perez L. H., Butler M., Creasey T., Dzink-Fox J., Gounarides J., Petit S., Ropenga A., Ryder N., Smith K., Smith P., Parkinson S. J.
ISSN
1932-6203
Publication state
Published
Issued date
2010
Volume
5
Number
6
Pages
e10915
Language
english
Notes
1932-6203
Perez, Laurent-Herve
Butler, Matt
Creasey, Tammy
Dzink-Fox, JoAnn
Gounarides, John
Petit, Stephanie
Ropenga, Anna
Ryder, Neil
Smith, Kathryn
Smith, Philip
Parkinson, Scott J
Journal Article
Research Support, Non-U.S. Gov't
PLoS One. 2010 Jun 1;5(6):e10915. doi: 10.1371/journal.pone.0010915.
Abstract
BACKGROUND: A homeostatic relationship with the intestinal microflora is increasingly appreciated as essential for human health and wellbeing. Mutations in the leucine-rich repeat (LRR) domain of Nod2, a bacterial recognition protein, are associated with development of the inflammatory bowel disorder, Crohn's disease. We investigated the molecular mechanisms underlying disruption of intestinal symbiosis in patients carrying Nod2 mutations. METHODOLOGY/PRINCIPAL FINDINGS: In this study, using purified recombinant LRR domains, we demonstrate that Nod2 is a direct antimicrobial agent and this activity is generally deficient in proteins carrying Crohn's-associated mutations. Wild-type, but not Crohn's-associated, Nod2 LRR domains directly interacted with bacteria in vitro, altered their metabolism and disrupted the integrity of the plasma membrane. Antibiotic activity was also expressed by the LRR domains of Nod1 and other pattern recognition receptors suggesting that the LRR domain is a conserved anti-microbial motif supporting innate cellular immunity. CONCLUSIONS/SIGNIFICANCE: The lack of anti-bacterial activity demonstrated with Crohn's-associated Nod2 mutations in vitro, supports the hypothesis that a deficiency in direct bacterial killing contributes to the association of Nod2 polymorphisms with the disease.
Keywords
Bacteria/*drug effects, Crohn Disease/*genetics/microbiology, Humans, *Mutation, Nod2 Signaling Adaptor Protein/*pharmacology, Recombinant Proteins/pharmacology
Create date
04/09/2020 19:03
Last modification date
07/09/2020 5:26
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