The lipopolysaccharide from Capnocytophaga canimorsus reveals an unexpected role of the core-oligosaccharide in MD-2 binding.

PLoS Pathogens
Simon IttigUlrich Zähringer

Abstract

Capnocytophaga canimorsus is a usual member of dog's mouths flora that causes rare but dramatic human infections after dog bites. We determined the structure of C. canimorsus lipid A. The main features are that it is penta-acylated and composed of a "hybrid backbone" lacking the 4' phosphate and having a 1 phosphoethanolamine (P-Etn) at 2-amino-2-deoxy-d-glucose (GlcN). C. canimorsus LPS was 100 fold less endotoxic than Escherichia coli LPS. Surprisingly, C. canimorsus lipid A was 20,000 fold less endotoxic than the C. canimorsus lipid A-core. This represents the first example in which the core-oligosaccharide dramatically increases endotoxicity of a low endotoxic lipid A. The binding to human myeloid differentiation factor 2 (MD-2) was dramatically increased upon presence of the LPS core on the lipid A, explaining the difference in endotoxicity. Interaction of MD-2, cluster of differentiation antigen 14 (CD14) or LPS-binding protein (LBP) with the negative charge in the 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo) of the core might be needed to form the MD-2 - lipid A complex in case the 4' phosphate is not present.

References

Apr 1, 1976·American Journal of Clinical Pathology·R A Bobo, E J Newton
Jan 1, 1990·Annual Review of Biochemistry·C R Raetz
Jan 14, 1989·BMJ : British Medical Journal·A J WestwellD N Hutchinson
May 15, 1974·European Journal of Biochemistry·G RosenfelderO Westphal
Apr 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·J PuginP S Tobias
Jan 1, 1993·Advances in Immunology·R J Ulevitch
Feb 1, 1994·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·E T RietschelF Di Padova
Feb 1, 1996·Journal of Molecular Graphics·W HumphreyK Schulten
Jul 1, 1996·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·C PersW Frederiksen
Sep 1, 1997·Nucleic Acids Research·S F AltschulD J Lipman
Oct 23, 1997·Proceedings of the National Academy of Sciences of the United States of America·T KiyonoM Ishibashi
Nov 20, 1998·The Journal of Infection·P BlancheD Sicard
Feb 27, 1999·Current Opinion in Immunology·R J Ulevitch, P S Tobias
Jun 8, 1999·The Journal of Experimental Medicine·R ShimazuM Kimoto
May 1, 2001·Clinical and Diagnostic Laboratory Immunology·K TanamotoS Azumi
Jun 5, 2002·Annual Review of Biochemistry·Christian R H Raetz, Chris Whitfield
Jul 18, 2003·Journal of Computational Chemistry·H Bernhard Schlegel
Jan 1, 1954·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·G GOMORI
Mar 1, 1954·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·R C BAHN, D GLICK
Apr 1, 1954·The Journal of Pathology and Bacteriology·I M DAWSON
Nov 25, 2003·Advances in Protein Chemistry·Jay W Ponder, David A Case
Jul 21, 2004·Journal of Computational Chemistry·Alexander D Mackerell
Dec 21, 2004·Nature Reviews. Microbiology·Samuel I MillerMartin W Bader
Oct 4, 2005·Journal of Computational Chemistry·David A CaseRobert J Woods
Dec 3, 2005·European Journal of Mass Spectrometry·Anna Kondakov, Buko Lindner
Feb 10, 2006·The Journal of Biological Chemistry·Xiaoyuan WangChristian R H Raetz
Feb 16, 2006·Journal of Lipid Research·Christian R H RaetzEdward A Dennis
Feb 24, 2006·Emerging Infectious Diseases·J Michael JandaWill S Probert
Aug 1, 1978·Proceedings of the National Academy of Sciences of the United States of America·S K MaitraL B Guze
May 11, 2006·Chemical Reviews·Stewart A Adcock, J Andrew McCammon
Jan 6, 2007·The Journal of Infectious Diseases·Hwain ShinGuy R Cornelis
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Xiaoyuan WangChristian R H Raetz
Mar 17, 2007·Annual Review of Biochemistry·Christian R H RaetzRussell E Bishop
Jun 5, 2007·Glycobiology·Shanta M ZimmerDavid S Stephens

❮ Previous
Next ❯

Citations

Mar 24, 2015·Expert Review of Vaccines·Afshin Zariri, Peter van der Ley
Sep 1, 2015·Molecular Immunology·Daiva M MattisDavid M Kranz
Jun 21, 2014·BioMed Research International·Nitha C MulakkalIoannis P Nezis
Oct 1, 2015·Emerging Microbes & Infections·Francesco RenziGuy Richard Cornelis
Apr 2, 2015·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·T Butler
May 30, 2015·Genome Announcements·Pablo ManfrediGuy R Cornelis
Dec 16, 2016·Scientific Reports·Francesco RenziGuy R Cornelis
Sep 20, 2017·Journal of the American Society for Mass Spectrometry·Adriana C CasabuonoAlicia S Couto
Dec 9, 2015·Infection and Immunity·Francesco RenziSimon J Ittig
Jul 6, 2014·The Journal of Biological Chemistry·Ulrich ZähringerGuy R Cornelis
Dec 26, 2019·Innate Immunity·Jorge Lozano-AponteChristian Alexander
Jun 27, 2019·Case Reports in Infectious Diseases·Moritz HundertmarkBenjamin Sasko
Dec 29, 2016·Journal of Thrombosis and Haemostasis : JTH·K HackG R Cornelis
Dec 13, 2017·Der Anaesthesist·K FeigeJ T Lutz

❮ Previous
Next ❯

Methods Mentioned

BETA
x-ray crystallography
acylation
FCS
NMR
acetylation
scraping
PMA
ELISA
transfection

Software Mentioned

MultiGauge
ProDy
AMBER11
InvivoGen
Topspin
ORCA2
GAUSSIAN09
MPI
VMD
MMPBSA

Related Concepts

Related Feeds

Blood Clotting Disorders

Thrombophilia includes conditions with increased tendency for excessive blood clotting. Blood clotting occurs when the body has insufficient amounts of specialized proteins that make blood clot and stop bleeding. Here is the latest research on blood clotting disorders.

Aminoglycosides

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Aminoglycosides (ASM)

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Campylobacteriosis (ASM)

Campylobacteriosis is caused by the bacteria Campylobacter jejuni and is a common cause of gastroenteritis in humans. Discover the latest research on Campylobacteriosis here.