Professor David Holden

Salmonella pathogenesis

Our group studies molecular aspects of Salmonella pathogenesis, focusing in particular on the functions of a specialized multi-protein machine known as a type III secretion system, which translocates virulence proteins (effectors) from intracellular bacteria across phagosomal membranes into host cells. These effectors help to create a specialised compartment - the Salmonella-containing vacuole (SCV), which permits bacterial replication in host cells. At least three effectors are involved in regulating vacuolar membrane dynamics. Other effectors promote and antagonize ubiquitination and phosphorylation in host signaling pathways to modulate host immune responses. Our research involves a multi-disciplinary approach, using molecular genetics, biochemistry and cell biology, to understand how the collective action of effectors enables the intracellular replication of the pathogen.

Recently we have developed methods for analyzing the dynamics of bacterial replication at the single cell level, both in cultured cells and in vivo. We discovered that a surprisingly large proportion of the bacterial inoculum fails to replicate, but enters a viable non-replicating state. The approach is being extended to study non-replicating bacteria associated with chronic infections caused by other pathogens.

Further information: http://www1.imperial.ac.uk/departmentofmedicine/divisions/infectiousdiseases/microbiology/stm/

Contact details:

Tel: +44 (0)20 7594 3073
Email: d.holden@imperial.ac.uk