A Family of Salmonella Type III Secretion Effector Proteins Selectively Targets the NF-κB Signaling Pathway to Preserve Host Homeostasis

PLoS Pathogens

Maria Lara-Tejero¹  Hui Sun¹  Jana Kamanova¹  Jorge E. Galán¹ 

[1] Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut, United States of America

关键词: Salmonella typhimurium;    Transcription factors;    Mutant strains;    Plasmid construction;    Cytokines;    STAT proteins;    Inflammation;    Transfection;   

DOI  :  10.1371/journal.ppat.1005484

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Microbial infections usually lead to host innate immune responses and inflammation. These responses most often limit pathogen replication although they can also result in host-tissue damage. The enteropathogenic bacteria Salmonella Typhimurium utilizes a type III secretion system to induce intestinal inflammation by delivering specific effector proteins that stimulate signal transduction pathways resulting in the production of pro-inflammatory cytokines. We show here that a family of related Salmonella Typhimurium effector proteins PipA, GogA and GtgA redundantly target components of the NF-κB signaling pathway to inhibit transcriptional responses leading to inflammation. We show that these effector proteins are proteases that cleave both the RelA (p65) and RelB transcription factors but do not target p100 (NF-κB2) or p105 (NF-κB1). A Salmonella Typhimurium strain lacking these effectors showed increased ability to stimulate NF-κB and increased virulence in an animal model of infection. These results indicate that bacterial pathogens can evolve determinants to preserve host homeostasis and that those determinants can reduce the pathogen’s virulence.

【 授权许可】

CC BY