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Molecular and Genetic Study of the human infections by Capnocytophaga canimorsus

Objective

"Capnocytophaga canimorsus are Gram-negative bacteria from the normal oral flora of dogs, which cause rare but severe infections in humans that have been bitten or simply licked. The most common syndrome is fulminant septicemia with peripheral gangrene. Mortality reaches 40 % in spite of antibiotherapy and amputations. My laboratory pioneered recently the study of this new pathogen. We engineered genetic tools, sequenced and annotated the genome and determined the surface proteome of a strain isolated from a fatal infection. This showed that C. canimorsus have abundant surface-exposed lipoproteins forming a new kind of feeding complexes, some of them specialized in deglycosylating glycoproteins from the host. This property allows C. canimorsus to feed by grazing oligosaccharides at the surface of human cells. The present research program aims at characterizing these deglycosylating complexes, unravelling their role in neutralizing the innate immunity and promoting growth within the host and finally characterizing their assembly at the bacterial surface. Genomic comparisons will help defining which of these many complexes play a critical role in human pathogenesis. Besides this, the lipopolysaccharide structure will be determined and genetically manipulated to understand its low endotoxicity and small anti-inflammatory effectors present in the culture supernatant of C. canimorsus will be identified. Growth in human blood of wild type and mutant strains will be monitored by isothermal microcalorimetry in the hope of developing a surrogate of animal model. Such a ""virulence"" model would allow to address the question whether all dog's strains are equally dangerous for humans. It would also open an avenue for testing differences in individual human susceptibility. All this knowledge will give new insights in this emerging pathogen and might lead to prevention of the disease caused by C. canimorsus"

Call for proposal

ERC-2011-ADG_20110310
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Host institution

UNIVERSITE DE NAMUR ASBL
Address
Rue De Bruxelles 61
5000 Namur
Belgium
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 473 338
Principal investigator
Guy Richard Cornelis (Prof.)
Administrative Contact
Christelle Saout (Dr.)

Beneficiaries (1)

UNIVERSITE DE NAMUR ASBL
Belgium
EU contribution
€ 1 473 338
Address
Rue De Bruxelles 61
5000 Namur
Activity type
Higher or Secondary Education Establishments
Principal investigator
Guy Richard Cornelis (Prof.)
Administrative Contact
Christelle Saout (Dr.)