RRC ID 51429
Author Tjahjono E, Kirienko NV.
Title A conserved mitochondrial surveillance pathway is required for defense against Pseudomonas aeruginosa.
Journal PLoS Genet
Abstract All living organisms exist in a precarious state of homeostasis that requires constant maintenance. A wide variety of stresses, including hypoxia, heat, and infection by pathogens perpetually threaten to imbalance this state. Organisms use a battery of defenses to mitigate damage and restore normal function. Previously, we described a Caenorhabditis elegans-Pseudomonas aeruginosa assay (Liquid Killing) in which toxicity to the host is dependent upon the secreted bacterial siderophore pyoverdine. Although pyoverdine is also indispensable for virulence in mammals, its cytological effects are unclear. We used genetics, transcriptomics, and a variety of pathogen and chemical exposure assays to study the interactions between P. aeruginosa and C. elegans. Although P. aeruginosa can kill C. elegans through at least 5 different mechanisms, the defense responses activated by Liquid Killing are specific and selective and have little in common with innate defense mechanisms against intestinal colonization. Intriguingly, the defense response utilizes the phylogenetically-conserved ESRE (Ethanol and Stress Response Element) network, which we and others have previously shown to mitigate damage from a variety of abiotic stresses. This is the first report of this networks involvement in innate immunity, and indicates that host innate immune responses overlap with responses to abiotic stresses. The upregulation of the ESRE network in C. elegans is mediated in part by a family of bZIP proteins (including ZIP-2, ZIP-4, CEBP-1, and CEBP-2) that have overlapping and unique functions. Our data convincingly show that, following exposure to P. aeruginosa, the ESRE defense network is activated by mitochondrial damage, and that mitochondrial damage also leads to ESRE activation in mammals. This establishes a role for ESRE in a phylogenetically-conserved mitochondrial surveillance system important for stress response and innate immunity.
Volume 13(6)
Pages e1006876
Published 2017-6-1
DOI 10.1371/journal.pgen.1006876
PMID 28662060
PMC PMC5510899
MeSH Animals Basic-Leucine Zipper Transcription Factors / genetics Caenorhabditis elegans / genetics Caenorhabditis elegans / microbiology Host-Pathogen Interactions / genetics* Immunity, Innate / genetics* Mitochondria / genetics* Oligopeptides / genetics Pseudomonas aeruginosa / genetics* Pseudomonas aeruginosa / pathogenicity Siderophores / genetics Signal Transduction Stress, Physiological / genetics Virulence Factors / genetics
IF 5.175
Times Cited 12
C.elegans tm1359 tm2807 tm4248 tm5421