A Conserved Mitochondrial Surveillance Pathway Is Required for Defense against Pseudomonas aeruginosa

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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Tjahjono E, Kirienko NV