Selective Inhibition of Type III Secretion Activated Signaling by the Salmonella Effector AvrA e1000595

• Published in: PLoS pathogens Vol. 5; no. 9
• Main Authors: Du, Fangyong, Galán, Jorge E
• Format: Journal Article
• Language: English
• Published: San Francisco Public Library of Science 01-09-2009
• Subjects: Bacterial proteins; Bacteriology; Kinases; Salmonella
• ISSN: 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1000595

Salmonella enterica utilizes a type III secretion system (TTSS) encoded in its pathogenicity island 1 to mediate its initial interactions with intestinal epithelial cells, which are characterized by the stimulation of actin cytoskeleton reorganization and a profound reprogramming of gene expression. These responses result from the stimulation of Rho-family GTPases and downstream signaling pathways by specific effector proteins delivered by this TTSS. We show here that AvrA, an effector protein of this TTSS, specifically inhibits the Salmonella-induced activation of the JNK pathway through its interaction with MKK7, although it does not interfere with the bacterial infection-induced NF-κB activation. We also show that AvrA is phosphorylated at evolutionary conserved residues by a TTSS-effector-activated ERK pathway. This interplay between effector proteins delivered by the same TTSS highlights the remarkable complexity of these systems.