21 February 2012
Prof Vassilis Koronakis' team have uncovered a new path by which the bacterial pathogen Salmonella triggers its uptake into intestinal cells to initiate infection. They reveal this week in Cell Host & Microbe that pathogen and host guanine nucleotide exchange factors (GEFs) cooperate to control host cell WAVE complex regulation and pathogen macropinocytosis (picture shows Salmonella (red) engulfed by macropinosome).
Eukaryotic cells contain a dynamic network of actin filaments that are assembled and disassembled to drive fundamental
- Fig: Salmonella (blue) triggering Arf-enriched membrane ruffles (red)
This novel cooperation between bacterial and host GEFs introduces a new layer of complexity in the mechanisms used by pathogens to control the host actin cytoskeleton, which has profound implications actin-dependent cellular processes in both health and disease.
- Humphreys D, Davidson AC, Hume PJ, Koronakis V (2012). Salmonella effector SopE and host GEF ARNO cooperate to recruit and activate WAVE to trigger bacterial invasion. Cell Host Microbe 11: 1-11
- Koronakis V, Hume PJ, Humphreys D, Liu T, Jensen O and McGhie EJ (2011). WAVE regulatory complex activation by cooperating GTPases Arf and Rac1. Proc Natl Acad Sci 35:14449-54
- Smith K, Humphreys D, Hume PJ, Koronakis V (2010). Enteropathogenic Escherichia coli recruits the cellular inositol phosphatase SHIP2 to regulate actin-pedestal formation. Cell Host Microbe 1: 13-24.
- Humphreys D, Hume, PJ, Koronakis V (2009). Salmonella effector SptP dephosphorylates host AAA+ ATPase VCP to promote development of its intracellular replicative niche. Cell Host Microbe, 5:225-33.
For more information contact Professor Vassilis Koronakis (vk103@cam.ac.uk). This work was funded by the Wellcome Trust and the Isaac Newton Trust