Presentation/Session Information

Session Information

Session Title: Physiology: Metabolism and Pathogenesis Session Type: Parallel
Session Location: Grand Horizon Ballroom Session Time: Sat, Jun 27 8:30AM - 11:30AM

Presentation Information

Program Number: 160 Presentation Time: 10:42AM - 10:54AM

Presentation Content

Mitophagy and hypoxic response protect C. elegans against P. aeruginosa pathogenesis.Natalia Kirienko 1,2, Daniel Kirienko 1,2, Fred Ausubel 1,2, Gary Ruvkun 1,2. 1)Dept Molecular Biol, Mass General Hospital, Boston, MA; 2)Harvard Medical School, Boston, MA

In the arms race of bacterial pathogenesis, bacteria produce an array of toxins and virulence factors that disrupt core host processes. Hosts mitigate the ensuing damage by responding with immune countermeasures. The iron-binding siderophore pyoverdin is a key virulence mediator of the human pathogen Pseudomonas aeruginosa, but its pathogenic mechanism has not been established. Here we demonstrate that pyoverdin enters Caenorhabditis elegans and that it is sufficient to mediate host killing. In addition, a screen of small molecules that protect C. elegans from P. aeruginosa virulence identified a number of hits that interfere with either the function or the biosynthesis of pyoverdin. This confirms the importance of this virulence factor as well as offer possibilities for developing anti-Pseudomonal therapies.

We show that exposure to pyoverdin disrupts mitochondrial homeostasis and triggers mitophagy both in C. elegans and mammalian cells. Disruption of iron homeostasis also causes stabilization of HIF-1, triggering a hypoxic response that contributes to the immune defense against P. aeruginosa. Finally, we show that activation of mitophagy provides protection both against the extracellular pathogen P. aeruginosa and to treatment with a xenobiotic chelator, phenanthroline, in C. elegans. Although autophagic machinery has been shown to target intracellular bacteria for degradation (a process known as xenophagy), our report establishes a role for authentic mitochondrial autophagy in the innate immune defense against P. aeruginosa.

Please note: Abstract shown here should NOT be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.

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