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Study of the molecular mechanisms of Yersinia and Capnocytophaga infections

English title Study of the molecular mechanisms of Yersinia and Capnocytophaga infections
Applicant Cornelis Guy Richard
Number 113333
Funding scheme Project funding (Div. I-III)
Research institution Abteilung Mikrobiologie Biozentrum Universität Basel
Institution of higher education University of Basel - BS
Main discipline Experimental Microbiology
Start/End 01.01.2007 - 31.12.2009
Approved amount 834'000.00
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All Disciplines (2)

Discipline
Experimental Microbiology
Medical Microbiology

Keywords (7)

microbial pathogenesis; infection; yersinia; protein translocation; type-III secretion; capnocytophaga; dog bites

Lay Summary (English)

Lead
Lay summary
Our research aims at understanding the molecular aspects of bacterial infections and, in particular how bacterial pathogens neutralize macrophages, sentinels of the innate immune system. The goal is to shape new concepts and identify new targets for future prevention and treatment of infectious diseases.Many bacteria, including Yersinia, the agents of plague and human enterocolitis, have the capacity to inject "effector" proteins into the cytosol of animal, plant or insect cells, a process called "type-III secretion" (T3S). The effectors disarm or reprogram the target cell by sabotaging or hijacking the cellular signaling network. The T3S apparatus, called injectisome, is a complex nanosyringe made of more than 25 different proteins. It consists of a transmembrane basal body and a ca 60-nm long needle protruding from the surface. The injectisome is one of the most complex bacterial nanomachines known. It represents a remarkable model of bio nanomachines and it is also an excellent target for vaccines or drugs. For instance, we have discovered that the best protective antigen against plague forms the structure at the needle tip. Presently, we focus on how the 25 different proteins of the Yersinia injectisome assemble in an ordered way and how this machine controls its needle length.We also study Capnocytophaga canimorsus, a bacterium commonly found in dog's mouths and responsible for fatal septicemia or meningitis in humans after dog bites or licks. Our goal is to understand these dramatic cases and to find ways to prevent them. In addition, this study of C. canimorsus shed light on the relation between commensals and their host and illustrates how thin is the line separating a commensal from a pathogen. We have established that these bacteria are resistant to the bacteridal activity of complement, as well as to phagocytosis by macrophages and by polymorphonuclear leukocytes. We also found that a few strains of C. canimorsus can actively block the release of NO by activated macrophages and the killing of phagocytosed E. coli. In 2008, we determined the prevalence of C. canimorsus in dogs and the occurrence of these hypothetical virulence factors among dog strains. Sixty-one C. canimorsus strains could be retrieved from the saliva from 106 dogs.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Associated projects

Number Title Start Funding scheme
128659 Study of the molecular mechanisms of Yersinia and Capnocytophaga infections 01.01.2010 Project funding (Div. I-III)
125110 Unravelling the structure of the Yersinia Ysc injectisome 01.07.2009 Sinergia
65393 Molecular and cell biology of the Yersinia infections 01.01.2002 Project funding (Div. I-III)

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