Document Detail


The lipid A phosphate position determines differential host Toll-like receptor 4 responses to phylogenetically related symbiotic and pathogenic bacteria.
MedLine Citation:
PMID:  20974832     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The human symbiont Bacteroides thetaiotaomicron promotes intestinal function and health, whereas the phylogenetically related pathogen Porphyromonas gingivalis is associated with the chronic oral inflammatory disease periodontitis. Although both B. thetaiotaomicron and P. gingivalis synthesize lipopolysaccharides (LPS) consisting of penta-acylated, monophosphorylated lipid A in addition to immunologically silent, nonphosphorylated lipid A, they elicit strikingly distinct Toll-like receptor 4 (TLR4) responses. We show that the phosphate position of penta-acylated, monophosphorylated lipid A is a key feature for determining the differential TLR4 responses elicited by these evolutionarily related bacteria. B. thetaiotaomicron produces TLR4-stimulatory lipid A bearing a 1-phosphate, in contrast to P. gingivalis, which produces TLR4-evasive lipid A bearing a 4'-phosphate. Confirming these observations, recombinant Escherichia coli LPS containing penta-acylated, 1-phosphorylated lipid A is more TLR4 stimulatory than LPS containing 4'-phosphorylated lipid A. The specific capacity of a Gram-negative bacterium to alert or evade the host innate immune defense system through TLR4-dependent signaling is currently recognized as a critical aspect defining the relationship between the host and the bacterium. We propose that the distinct lipid A phosphate positions observed for the B. thetaiotaomicron and P. gingivalis LPS contributes to the manifestation of these bacteria as commensal or pathogen within the human host.
Authors:
Stephen R Coats; Alex B Berezow; Thao T To; Sumita Jain; Brian W Bainbridge; Karim P Banani; Richard P Darveau
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-10-25
Journal Detail:
Title:  Infection and immunity     Volume:  79     ISSN:  1098-5522     ISO Abbreviation:  Infect. Immun.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2010-12-23     Completed Date:  2011-01-25     Revised Date:  2011-08-01    
Medline Journal Info:
Nlm Unique ID:  0246127     Medline TA:  Infect Immun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  203-10     Citation Subset:  IM    
Affiliation:
Department of Periodontics, School of Dentistry, University of Washington, 1959 NE Pacific St., HSB, Box 357444, Seattle, WA 98195, USA. scoats@u.washington.edu
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MeSH Terms
Descriptor/Qualifier:
Bacteroides / genetics*,  metabolism
Carbohydrate Conformation
Escherichia coli / genetics*,  metabolism
Gene Expression Regulation / physiology
HEK293 Cells
Host-Pathogen Interactions
Humans
Lipid A / chemistry*,  metabolism
Phylogeny
Porphyromonas gingivalis / genetics*,  metabolism
Symbiosis
Toll-Like Receptor 4 / genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
DE012768/DE/NIDCR NIH HHS; DE018274/DE/NIDCR NIH HHS
Chemical
Reg. No./Substance:
0/Lipid A; 0/TLR4 protein, human; 0/Toll-Like Receptor 4
Comments/Corrections

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