The Annexin A2/p11 complex is required for efficient invasion of Salmonella Typhimurium in epithelial cells.
The facultative intracellular pathogen, Salmonella enterica, triggers its own uptake into non-phagocytic epithelial cells. Invasion is dependent on a type 3 secretion system (T3SS), which delivers a cohort of effector proteins across the plasma membrane where they induce dynamic actin-driven ruffling of the membrane and ultimately, internalization of the bacteria into a modified phagosome. In eukaryotic cells, the calcium- and phospholipid-binding protein Annexin A2 (AnxA2) functions as a platform for actin remodelling in the vicinity of dynamic cellular membranes. AnxA2 is mostly found in a stable heterotetramer, with p11, which can interact with other proteins such as the giant phosphoprotein AHNAK. We show here that AnxA2, p11 and AHNAK are required for T3SS-mediated Salmonella invasion of cultured epithelial cells and that the T3SS effector SopB is required for recruitment of AnxA2 and AHNAK to Salmonella invasion sites. Altogether this work shows that, in addition to targeting Rho-family GTPases, Salmonella can intersect the host cell actin pathway via AnxA2.
Salmonella Host-Cell Interactions Section, Laboratory of Intracellular Parasites, National Institute of Allergy and Infectious Disease, National Institutes of Health, Hamilton, MT, 59840, USA.
Carrie
C
Jolly
Seth
S
Winfree
Bryan
B
Hansen
Olivia
O
Steele-Mortimer
D017306:Annexin A2 / Q000378:metabolism*; D004705:Endocytosis; D004847:Epithelial Cells / Q000382:microbiology*; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D009418:S100 Proteins / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000502:physiology*; D000099248:S100 Calcium Binding Protein A10
D017306:Annexin A2; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D009418:S100 Proteins; D000099248:S100 Calcium Binding Protein A10; C075176:AHNAK protein, human; C472822:ANXA2 protein, human