A Delicate Balance between Bacterial Iron and Reactive Oxygen Species Supports Optimal C. elegans Development

• Published in: Cell host & microbe 2019-09, Vol.26 (3), p.400-411.e3
• Main Authors: Zhang, Jingyan, Li, Xuhang, Olmedo, Maria, Holdorf, Amy D., Shang, Ye, Artal-Sanz, Marta, Yilmaz, L. Safak, Walhout, Albertha J.M.
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants - metabolism; C. elegans; Caenorhabditis elegans - genetics; Caenorhabditis elegans - growth & development; Caenorhabditis elegans - microbiology; Diet; E. coli; electron transport chain; Electron Transport Chain Complex Proteins - genetics; Escherichia coli - genetics; Escherichia coli - physiology; flux balance analysis; Gene Deletion; Host Microbial Interactions - physiology; iron; Iron - metabolism; metabolic network modeling; metabolism; Mitochondria; Mutation; reactive oxygen species; Reactive Oxygen Species - metabolism
• ISSN: 1931-3128; 1934-6069
• DOI: 10.1016/j.chom.2019.07.010

Iron is an essential micronutrient for all forms of life; low levels of iron cause human disease, while too much iron is toxic. Low iron levels induce reactive oxygen species (ROS) by disruption of the heme and iron-sulfur cluster-dependent electron transport chain (ETC). To identify bacterial metabolites that affect development, we screened the Keio Escherichia coli collection and uncovered 244 gene deletion mutants that slow Caenorhabditis elegans development. Several of these genes encode members of the ETC cytochrome bo oxidase complex, as well as iron importers. Surprisingly, either iron or anti-oxidant supplementation reversed the developmental delay. This suggests that low bacterial iron results in high bacterial ROS and vice versa, which causes oxidative stress in C. elegans that subsequently impairs mitochondrial function and delays development. Our data indicate that the bacterial diets of C. elegans provide precisely tailored amounts of iron to support proper development. [Display omitted] •A screen of E. coli mutants reveals bacterial genes essential for C. elegans development•This developmental delay can be rescued by anti-oxidants or iron supplementation•Low bacterial iron raises ROS production likely triggering oxidative stress in C. elegans Zhang et al. identify more than 200 E. coli deletion mutants that, when fed to C. elegans as diet, slow animal development. This phenotype can be rescued by iron or anti-oxidant supplementation, indicating that low bacterial iron causes oxidative stress in the animal, which in turn decelerates development.