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Molecular and cell biology of the Yersinia infections

Applicant Cornelis Guy Richard
Number 65393
Funding scheme Project funding (Div. I-III)
Research institution Abteilung Mikrobiologie Biozentrum Universität Basel
Institution of higher education University of Basel - BS
Main discipline Medical Microbiology
Start/End 01.01.2002 - 31.12.2006
Approved amount 1'128'333.00
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Keywords (9)

YERSINIA; YOPS; YOP P/J; YOP M; SYC; PORE; TYPE III; TRANSLOCATION; bonus-of-excellence

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 sohisticated bio nanomachines. Since many pathogenic bacteria are endowed with injectisomes, the Yersinia injectisome serves as a model for several infectious diseases. In particular, studies on Yersinia have shown that the injectisome could be a good target for chemotherapy. The objectives of the project were (i) to characterize by electron microscopy the injectisome and especially its terminal needle and to unravel the assembly process; (ii) to understand how the injectisome recognizes the proteins it injects; (iii) to understand how the injected proteins neutralize the host cells inflammatory response. We made two major findings published in the magazine "Science". First, we unraveled the mechanism by which bacteria control the length of the injectisome needle. Second, we discovered that the needle terminates with a tip structure made of a protein known as a protective antigen against plague. Besides this we demonstrated indirectly that the effectors travel through the needle in an unfolded state; we demonstrated that intrabacterial chaperones cover domains of the effectors that are involved in the targeting of the effectors inside animal cells and finally, we observed that Rho GTPases, the target of effectors YopE, YopT and YopO are involved in the maturation of Pro-IL1beta, a major pro-inflammatory cytokine.
Direct link to Lay Summary Last update: 21.02.2013

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Associated projects

Number Title Start Funding scheme
125110 Unravelling the structure of the Yersinia Ysc injectisome 01.07.2009 Sinergia
113333 Study of the molecular mechanisms of Yersinia and Capnocytophaga infections 01.01.2007 Project funding (Div. I-III)

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