• Guy Cornelis's Research Group
  • Guy Cornelis's Research Group
  • Guy Cornelis's Research Group
  • Guy Cornelis's Research Group

Research

The surface structures of C. canimorsus

The surface structures of bacteria are essential for their survival in the host and hence their pathogenicity.  They may represent a protection against the attack of complement and against phagocytosis but at the same time, they are an Achille's heel since the innate immunity system has evolved to recognize them to trigger inflammation.  We investigate the structure and role of the different surface structures of C. canimorsus, in collaboration with U. Zähringer (Borstel, D), I. Sadovskaya (Boulogne-sur-mer, F) and E. Maes (Lille, F).

 

Main publications:

- Renzi F., Zähringer U., Chandler C.E., Ernst R.K., Cornelis G.R., Ittig S.J. Modification of the 1-phosphate group during biosynthesis of Capnocytophaga canimorsus lipid A. Infection and Immunity. 2015 Dec 7. pii: IAI.01006-15.

- Zähringer U., Ittig S., Lindner B., Moll H., Schombel U., Gisch N., Cornelis G.R. NMR-based structural analysis of the complete rough-type lipopolysaccharide isolated from Capnocytophaga canimorsus. J Biol Chem. 2014 Aug 22;289(34):23963-76. doi: 10.1074/jbc.M114.571489. Epub 2014 Jul 2.

- Ittig, S., Lindner, B., Stenta, M., Manfredi, P., Zdorovenko, E., Knirel, Y., Dal Peraro, M., Cornelis, G.R, Zähringer, U. The Lipopolysaccharide from Capnocytophaga canimorsus Reveals an Unexpected Role of the Core-Oligosaccharide in MD-2 Binding. PLoS pathogens 2012, 8(5), e100266

- Shin H., Mally M., Meyer S., Fiechter C.,Paroz C., Zähringer U., Cornelis G.R. Resistance of Capnocytophaga canimorsus to killing by human complement and polymorphonuclear leukocytes. Infection and Immunity 2009, 77(6): 2262–2271. Epub Mar 23, 2009

 

Identification of new virulence factors: a genomic approach

Almost every dog harbours C. canimorsus in its mouth.  Nevertheless, the human infections are rare.  Are all the strains of C. canimorsus equally pathogenic for humans?  Do the strains isolated from infections have particular virulence factors? To address this question, we raised a collection of C. canimorsus strains isolated from human infections and from dogs mouths and we compare genomes.  This work, still in progress, led us to discover that a significant part of the C. canimorsus  strains are not pathogenic and even represent a new species Capnocytophaga canis  sp. nov..

 

Main publication:

- Renzi F., Dol M., Raymackers A., Manfredi P., Cornelis G.R. Only a subset of C. canimorsus strains is dangerous for humans. Emerg Microbes Infect. 2015 Aug;4(8):e48. doi: 10.1038/emi.2015.48. Epub 2015 Aug 19.

Interplay between C. canimorsus and the coagulation system

C. canimorsus sepsis is accompanied in up to 50% of the cases by skin manifestations, reaching from petechiae to purpura fulminans. The patients that develop severe sepsis and septic shock frequently suffer from disseminated intravascular coagulation (DIC) and consequently develop gangrene (8-13% of all cases) leading to amputations of fingers, arms or legs. One third of the autopsies carried out on deceased patients showed haemorrhage of the adrenal glands. Haemostasis is part of the innate immunity and a range of bacteria has the capacity to modulate this mechanism of defence. In view of these facts and the frequent occurrence of bleeding abnormalities during C. canimorsus infections we investigate the interactions between C. canimorsus and the human coagulation system.  This research is done in collaboration with the group of JM Dogné from the "Namur Medicine & Drug Innovation Center" (NAMEDIC).

 

Polysaccharide Utilization Loci (PUL) of C. canimorsus

A hallmark of Bacteroidetes is their remarkable capacity to harvest and metabolize all kinds of complex carbohydrates.  This property depends on specialized molecular complexes that are assembled at their surface.  The archetype of these complexes is the Starch Utilization System (Sus) of Bacteroides thetaiotaomicron.  These complexes are encoded in genomic loci called Polysaccharide Utilisation Loci (PUL). The genome of our reference strain C. canimorsus 5 contains13 PUL and these encode more than half of all proteins exposed at the bacterial surface.  We have discovered that PUL5 encodes the Glycoproteins Deglycosylation complex (Gpd) enabling the bacterium to harvest amino sugars from the surface of eukaryotic cells including phagocytes as well as from soluble serum proteins, such as IgG and transferrin.  The system is essential during the human infection because it represents for C. canimorsus the only source of amino sugars necessary for the synthesis of their peptidoglycan. We also discovered that PUL3 encodes a novel iron acquisition system allowing the bacterium to fetch iron from human transferrin. Finally, PUL9 encodes the Muc complex, devoted to mucin degradation, an abundant carbohydrate source for C. canimorsus in its ecological niche, the dog’s mouth.

 

Main publications:

- Renzi F., Manfredi P., Dol M., Fu J., Vincent S., Cornelis G.R. Glycan-foraging systems reveal the adaptation of Capnocytophaga canimorsus to the dog mouth. MBio. 2015 Mar 3;6(2):e02507. doi: 10.1128/mBio.02507-14.

- Manfredi, P., Lauber, F., Renzi, F., Hack, K., Hess, E. & Cornelis, G. R. New iron acquisition system in Bacteroidetes. Infection and Immunity. 83, 1, p. 300-310 11 p.

- Manfredi P., Renzi F., Mally M., Sauteur L., Schmaler M., Moes S., Jenö P., Cornelis G.R.  The genome and surface proteome of Capnocytophaga canimorsus reveal a key role of glycan foraging systems in host glycoproteins deglycosylation. Mol Microbiol. 2011 Aug;81(4):1050-60. doi:10.1111/j.1365-2958.2011.07750.x.

- Renzi F., Manfredi P., Mally M., Moes S., Jenö P., Cornelis G.R. The N-glycan Glycoprotein Deglycosylation Complex (Gpd) from Capnocytophaga canimorsus Deglycosylates Human IgG. PLoS Pathog. 2011 Jun;7(6):e1002118.

- Mally M., Shin H., Paroz C., Landmann R., Cornelis G.R.: Capnocytophaga canimorsus: a human pathogen feeding at the surface of epithelial cells and phagocytes. PloS Pathog. 2008 Sep 26;4(9):e1000164. doi: 10.1371/journal.ppat.1000164.

 

 

How are lipoproteins exported to the bacterial surface?

Lipoproteins represent the biggest part of the PUL-encoded complexes and they are surface-exposed. This abundance of exposed lipoproteins is one of the main characteristics of Bacteroidetes. In Proteobacteria, the vast majority of outer membrane lipoproteins is inserted in the inner leaflet of the outer membrane and thus faces the periplasm. Bacteroidetes are thus endowed with a new lipoproteins export pathway.  We work on unravelling this new pathway…