SopB-Mediated Recruitment of SNX18 Facilitates Salmonella Typhimurium Internalization by the Host Cell

Frontiers in Cellular and Infection Microbiology

Barnett, Timothy C.¹  Liebl, David²  Qi, Xiaying²  Zhe, Yang²  Teasdale, Rohan D.³ 

[1] Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, QLD, Australia;Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia;School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia

关键词: Salmonella;    macropinocytosis;    sorting nexin;    phosphoinositide;    host-pathogen interaction;   

DOI  :  10.3389/fcimb.2017.00257

学科分类：生物科学（综合）

来源: Frontiers

【 摘 要 】

To invade epithelial cells, Salmonella enterica serovar Typhimurium (S. Typhimurium) induces macropinocytosis through the action of virulence factors delivered across the host cell membrane via a type III secretion system. We show that after docking at the plasma membrane S. Typhimurium triggers rapid recruitment of cytosolic SNX18, a SH3-PX-BAR domain sorting nexin protein, to the bacteria-induced membrane ruffles and to the nascent Salmonella-containing vacuole. SNX18 recruitment required the inositol-phosphatase activity of the Salmonella effector SopB and an intact phosphoinositide-binding site within the PX domain of SNX18, but occurred independently of Rho-GTPases Rac1 and Cdc42 activation. SNX18 promotes formation of the SCV from the plasma membrane by acting as a scaffold to recruit Dynamin-2 and N-WASP in a process dependent on the SH3 domain of SNX18. Quantification of bacteria uptake revealed that overexpression of SNX18 increased bacteria internalization, whereas a decrease was detected in cells overexpressing the phosphoinositide-binding mutant R303Q, the ΔSH3 mutant, and in cells where endogenous levels of SNX18 were knocked-down. This study identifies SNX18 as a novel target of SopB and suggests a mechanism where S. Typhimurium engages host factors via local manipulation of phosphoinositide composition at the site of invasion to orchestrate the internalization process.

【 授权许可】

CC BY