Prof. Bernard C. Rossier

Ms Marie-Madeleine
+41 22 704 36 41


Chemin Rieu 17
P.O. Box 270
1211 Geneva 17
+41 22 704 36 36
+41 22 704 36 37


David W. Holden

Imperial College, London (UK)

Centre for Molecular Microbiology and Infection

Tuesday, October 23, 14:30 - 15:00

Intracellular biology of Salmonella

Following entry of Salmonella into host cells, this pathogen remains in a membrane-bound compartment called the Salmonella-containing vacuole. Bacteria sense the vacuolar environment and activate the expression of the SPI-2 type III secretion system (T3SS), to form the 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 effector translocation.
We are currently studying the functions of various effectors of the SPI-2 T3SS, which are 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. I will discuss some of our recent research on these topics and attempt to integrate this into the broader understanding of Salmonella pathogenesis.


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.