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Molecular and Genetic Study of the human infections by Capnocytophaga canimorsus

Final Report Summary - CAPCAN (Molecular and Genetic Study of the human infections by Capnocytophaga canimorsus)

Capnocytophaga canimorsus are common bacteria from dog's and cat's mouth. They cause rare but extremely severe infections in humans that have been in contact with a dog or a cat. The main syndrome is a septic shock with peripheral gangrene and the issue is often fatal. Half of the patients have reduced immune defenses due to splenectomy or liver damage. One goal of the project was to understand how these bacteria overcome the human innate immune defenses. We discovered that, by virtue of a capsular polysaccharide and a special lipopolysaccharide, they elicit relatively little inflammation and resist phagocytosis and killing by complement. We also unraveled how they acquire iron from human transferrin. We knew from previous work that C. canimorsus remove N-linked glycan chains from the proteins of their host. Here, we determined that this activity does not contribute to the immune evasion but it promotes growth of C. canimorsus in blood because it provides an amino sugar that is essential for the assembly of the cell wall. Another goal of the research was to find out whether all dog strains are equally dangerous for humans. Our results indicate that not every dog strain could provoke a human infection and we have identified a marker that could allow to identify potentially dangerous strains, opening an avenue for the prevention of these dramatic infections. In the frame of this work, we also identified a new protein export pathway in bacteria. This new pathway could have important applications in Biotechnology.