Mitophagy confers resistance to siderophore-mediated killing by Pseudomonas aeruginosa

作者：Kirienko Natalia V; Ausubel Frederick M; Ruvkun Gary^*

来源：Proceedings of the National Academy of Sciences, 2015, 112(6): 1821-1826.

DOI：10.1073/pnas.1424954112

• mitophagy
• Pseudomonas
• siderophore
• innate immunity
• C. elegans

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.

• 出版日期2015-2-10