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Updated: Apr 18, 2026
Replication of the Ordered, Nonredundant Library of Pseudomonas aeruginosa strain PA14 Transposon Insertion Mutants
Published on: May 4, 2018
Mitophagy confers resistance to siderophore-mediated killing by Pseudomonas aeruginosa
Natalia V Kirienko1, Frederick M Ausubel1, Gary Ruvkun2
1Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114; and Department of Genetics, Harvard Medical School, Boston, MA 02115.
Abstract:
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. Moreover, we show that iron chelation disrupts mitochondrial homeostasis and triggers mitophagy both in C. elegans and mammalian cells. Finally, we show that 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.
Insights
Pyoverdin from Pseudomonas aeruginosa causes host death by disrupting mitochondrial function. Mitophagy, a cellular cleanup process, protects against this pathogen and iron chelators.
Area of Science:
- Microbiology
- Cell Biology
- Immunology
Background:
- Bacteria like Pseudomonas aeruginosa use virulence factors to harm hosts.
- The siderophore pyoverdin is crucial for P. aeruginosa virulence but its mechanism is unclear.
- Host immune responses counteract bacterial virulence factors.
Purpose of the Study:
- To elucidate the pathogenic mechanism of pyoverdin.
- To investigate the role of mitochondrial homeostasis and mitophagy in host defense.
- To determine if mitophagy confers protection against P. aeruginosa infection.
Main Methods:
- Experiments were conducted using the model organism Caenorhabditis elegans.
- Mitochondrial homeostasis and mitophagy were assessed in response to iron chelation.
- Protection against P. aeruginosa and phenanthroline treatment was evaluated.
Main Results:
- Pyoverdin was shown to enter C. elegans and cause host killing.
- Iron chelation disrupted mitochondrial homeostasis and induced mitophagy in C. elegans and mammalian cells.
- Mitophagy conferred protection against P. aeruginosa and phenanthroline.
Conclusions:
- Pyoverdin's mechanism of virulence involves disruption of mitochondrial homeostasis.
- Mitophagy plays a significant role in innate immunity against P. aeruginosa.
- This study establishes mitochondrial autophagy as an immune defense against bacterial pathogens.
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