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| Status |
Public on Jun 20, 2017 |
| Title |
A Conserved Mitochondrial Surveillance Pathway Is Required for Defense against Pseudomonas aeruginosa |
| Organism |
Caenorhabditis elegans |
| Experiment type |
Expression profiling by array
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| Summary |
In the arms race of bacterial pathogenesis, bacteria produce an array of toxins and virulence factors that disrupt host processes while hosts respond with immune countermeasures. One key virulence mediator of the ubiquitous, opportunistic, extracellular pathogen Pseudomonas aeruginosa is the iron-binding siderophore pyoverdin (PMID:10722571;PMID: 8550201). The mechanisms used by pyoverdin to acquire iron from the host remain incompletely elucidated. Here we demonstrate that mitochondria represent an important target for iron acquisition and that exposure to this toxin results in loss of mitochondrial membrane potential, altered mitochondrial dynamics, and mitophagy in both Caenorhabditis elegans and mammalian cells. We also show that animal mitophagy protects the consequences of siderophore activity, conferring resistance to pyoverdin-mediated host killing. In C. elegans, the conserved autophagic genes bec-1/BECN1 and lgg-1/LC3, and the mitophagic regulator pink-1/PINK1 are required for iron chelator-elicited mitochondrial turnover and provide protection against iron sequestration by P. aeruginosa, likely by ameliorating the mitochondrial damage. While autophagic mechanisms have been implicated in the destruction of intracellular bacteria via a process called “xenophagy” (PMID: 24005326), our findings represent the first report of resistance to an extracellular pathogen being conferred by authentic autophagic activity that targets host organelles.
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| Overall design |
There are 21 samples total that comprise three biological replicates of glp-4(bn2) animals exposed to E.coli OP50 on solid NGM agar, E. coli OP50 on solid SK agar, E. coli OP50 in liquid LK media, P. aeruginosa PA14 on solid SK agar, P. aeruginosa PA14 in liquid LK media, DMSO + E.coli in liquid S Basal media, and 1 mM 1,10-phenanthroline + E.coli in liquid S Basal media for 8 hours at 25°C. Each biological replicate consists of glp-4 C. elegans animals in the young adult developmental stage.
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| Contributor(s) |
Kirienko NV |
| Citation(s) |
28662060 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| K22 AI110552 |
Mechanisms of Stimulating Innate Immunity |
RICE UNIVERSITY |
Natalia V. Kirienko |
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| Submission date |
Feb 27, 2014 |
| Last update date |
Sep 19, 2017 |
| Contact name |
Natalia V Kirienko |
| E-mail(s) |
kirienko@rice.edu
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| Organization name |
Rice University
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| Department |
BioSciences
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| Lab |
Kirienko
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| Street address |
6100 Main St. MS140
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| City |
Houston |
| State/province |
TX |
| ZIP/Postal code |
77005 |
| Country |
USA |
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| Platforms (1) |
| GPL200 |
[Celegans] Affymetrix C. elegans Genome Array |
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| Samples (21)
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| Relations |
| BioProject |
PRJNA239551 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE55422_RAW.tar |
40.4 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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