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The intracellular life of Salmonella

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David W. Holden- Imperial College London

When 20 May, 2013 from
11:00 am to 12:00 pm
Where Auditorium
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ITQB Seminar


Title: The intracellular life of Salmonella

Speaker: David W. Holden

Afilliation: Imperial College London

Host: Jaime Mota-Infection Biology Laboratory



Following entry of Salmonella into host cells, this pathogen resides in a membrane-bound compartment called the Salmonella-containing vacuole. Here, the bacteria either enter a viable non-replicating state or begin to divide. Replication is dependent on sensing the vacuolar environment and activation of the SPI-2 type III secretion system (T3SS). The T3SS comprises an envelope-spanning secretion system and associated translocon pore in the vacuolar membrane. Bacteria then sense the near-neutral pH of the host cell cytoplasm; this results in dissociation and degradation of a bacterial membrane-bound regulatory complex, which activates translocation of bacterial effector proteins into the host cell.

We are currently studying non-replicating intracellular Salmonella and the functions of various effectors, which have been implicated in several physiological activities, including avoidance of killing by macrophages, bacterial replication in a variety of host cell types, interference with immune signalling and the induction of cytotoxicity. In this talk I will discuss our recent progress in these areas.

Speaker's short biography:

David W. Holden invented signature-tagged mutagenesis (STM; also known as DNA barcoding), a widely used high-throughput functional genomics technique. Using STM his group identified numerous virulence genes of Streptococcus, Staphylococcus and Salmonella. They discovered the Salmonella SPI-2 type III secretion system and the functions of several of its effector proteins. The group currently researches bacterial virulence mechanisms, in particular those of Salmonella. David W. Holden is an EMBO member and Fellow of the American Academy of Microbiology, the Academy of Medical Sciences (UK) and the Royal Society (UK National Academy of Science). He co-founded the vaccine company Microscience, which was acquired in 2005 by Emergent Biosolutions.
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