Direct bacterial killing in vitro by recombinant Nod2 is compromised by Crohn's disease-associated mutations.
PLoS One
; 5(6): e10915, 2010 Jun 01.
Article
in En
| MEDLINE
| ID: mdl-20531959
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/PRINCIPALFINDINGS:
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Bacteria
/
Crohn Disease
/
Nod2 Signaling Adaptor Protein
/
Mutation
Type of study:
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
PLoS One
Journal subject:
CIENCIA
/
MEDICINA
Year:
2010
Document type:
Article
Affiliation country: