Frontier Leaders: Capnocytophaga canimorsus, cave canem!

Frontier Leaders Seminar

Title: Capnocytophaga canimorsus, cave canem!

Speaker: Guy R. Cornelis

Affiliation: Biozentrum, University of Basel, Switzerland and Dept. of Biology, University of Namur, Belgium

Abstract:

Capnocytophaga canimorsus are commensal Gram-negative bacteria from dog's mouth that cause rare but dramatic septicaemia in humans that have been licked, scratched or bitten.   Because of the presence of a low-inflammatory LPS, C. canimorsus 5 bacteria (Cc5) resist killing by complement and phagocytosis by human polymorphonuclear leukocytes. More surprisingly, C. canimorsus grow readily when they are in direct contact with mammalian cells, including phagocytes. To understand the mechanism behind this unusual property, the genome and the surface proteome of strain Cc5, cultivated onto HEK 293 cells were analyzed. The genome was found to contain 13 loci encoding a TonB-dependant porin and a few surface-exposed lipoproteins. The products of these genes resemble the archetypal starch utilization system (Sus) of Bacteroides tethaiotaomicron. Such loci are very common in Bacteroides spp and called polysaccharide utilization loci (PULs) because they are devoted to the metabolism of complex polysaccharides. Systematic deletions of the 13 loci of Cc5, revealed that the complex encoded by PUL5, one of the most abundant ones, is involved in foraging glycans from glycoproteins. It also contributed to survival in mice and conferred Cc5 the capacity to deglycosylate human IgG.  Deglycosylation is achieved by a large complex spanning the outer membrane and consisting of the five Gpd proteins and sialidase SiaC. GpdD, -G, -E and -F are surface-exposed outer membrane lipoproteins that contribute to the binding of glycoproteins at the bacterial surface while GpdG is a endo-β-N-acetylglucosaminidase cleaving the N-linked oligosaccharide after the first N-linked GlcNAc residue. GpdC, resembling a TonB-dependent OM transporter is presumed to import the oligosaccharide into the periplasm after its cleavage from the glycoprotein. The terminal sialic acid residue of the oligosaccharide is then removed by SiaC, a periplasm-exposed lipoprotein in direct contact with GpdC. Finally, most likely degradation of the oligosaccharide proceeds sequentially from the desialylated non reducing end by the action of periplasmic exoglycosidases, including β-galactosidases, β-N-Acetylhexosaminidases and α-mannosidases.  Another PUL encodes a mucinase, an expected function for a mouth commensal. However, a third one, present most clinical isolates but in only 50 % of dog strains turned out to encode a system scavenging iron from human transferrin.  This represents a new type of iron acquisition system in bacteria and a clear virulence determinant.


Biography

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