N^ε-fatty acylation of multiple membrane-associated proteins by Shigella IcsB effector to modulate host function.

ABSTRACT: Shigella flexneri, an intracellular Gram-negative bacterium causative for shigellosis, employs a type III secretion system to deliver virulence effectors into host cells. One such effector, IcsB, is critical for S. flexneri intracellular survival and pathogenesis, but its mechanism of action is unknown. Here, we discover that IcsB is an 18-carbon fatty acyltransferase catalysing lysine N^ε-fatty acylation. IcsB disrupted the actin cytoskeleton in eukaryotes, resulting from N^ε-fatty acylation of RhoGTPases on lysine residues in their polybasic region. Chemical proteomic profiling identified about 60 additional targets modified by IcsB during infection, which were validated by biochemical assays. Most IcsB targets are membrane-associated proteins bearing a lysine-rich po

SUBMITTER: Liu W 

PROVIDER: S-EPMC6466622 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature