IpaB Ion Channels Induce Pyroptosis in Macrophages
Lidija Senerovic, Anna Brotcke Zumsteg and Michael Kolbe
from: Shigella: Molecular and Cellular Biology (Edited by: William D. Picking and Wendy L. Picking). Caister Academic Press, U.K. (2016) Pages: 139-150.
The Gram-negative bacterium Shigella flexneri invades the colonic epithelium and causes bacillary dysentery. For successful infection, S. flexneri requires many effector proteins secreted via a Type three secretion system (T3SS). The effector protein IpaB is conserved in many medically important Gram-negative bacteria and is an essential virulence factor with multiple roles in S. flexneri infection. S. flexneri requires IpaB to invade host cells, escape from the phagosome and induce macrophage cell death. The mechanistic details regarding how IpaB functions have recently been elucidated. Secreted IpaB spontaneously oligomerizes and inserts into the plasma membrane of target cells. IpaB oligomers form channels selective for small monovalent cations with optimal activity at an acidic pH. After internalization, IpaB channels permit potassium flux inside macrophage vacuoles causing the disruption of the endolysosomal membranes. Vacuolar leakage is followed by an IPAF-dependent activation of caspase-1 and macrophage death. Mechanistic insights gained from IpaB studies with host cells may be extended to homologues from other medically important enteropathogenic bacteria and could contribute not only to understanding the conserved mechanisms of T3SS dependent infections, but also provide the solutions to fight them read more ...