Selenium-Enriched E. coli Bacteria Mitigate the Age-Associated Degeneration of Cholinergic Neurons in C. elegans.

Selenium (Se) is an essential trace element for humans and animals, but high-dose supplementation with Se compounds, most notably selenite, may exert cytotoxic and other adverse effects. On the other hand, bacteria, including Escherichia coli (E. coli), are capable of reducing selenite to red elemental Se that may serve as a safer Se source. Here, we examined how a diet of Se-enriched E. coli bacteria affected vital parameters and age-associated neurodegeneration in the model organism Caenorhabditis elegans (C. elegans). The growth of E. coli OP50 for 48 h in medium supplemented with 1 mM sodium selenite resulted in reddening of the bacterial culture, accompanied by Se accumulation in the bacteria. Compared to nematodes supplied with the standard E. coli OP50 diet, the worms fed on Se-enriched bacteria were smaller and slimmer, even though their food intake was not diminished. Nevertheless, given the choice, the nematodes preferred the standard diet. The fecundity of the worms was not affected by the Se-enriched bacteria, even though the production of progeny was somewhat delayed. The levels of the Se-binding protein SEMO-1, which serves as a Se buffer in C. elegans, were elevated in the group fed on Se-enriched bacteria. The occurrence of knots and ruptures within the axons of cholinergic neurons was lowered in aged nematodes provided with Se-enriched bacteria. In conclusion, C. elegans fed on Se-enriched E. coli showed less age-associated neurodegeneration, as compared to nematodes supplied with the standard diet.

SEMO-1, a novel methanethiol oxidase in Caenorhabditis elegans, is a pro-aging factor conferring selective stress resistance.

Methanethiol is a toxic gas produced through bacterial degradation of sulfur-containing amino acids. Applying a novel enzymatic assay, we here identified a methanethiol oxidase (MTO) that catalyzes the degradation of methanethiol in the nematode Caenorhabditis elegans (C. elegans). The corresponding protein, Y37A1B.5, previously characterized as a C. elegans ortholog of human selenium-binding protein 1 (SELENBP1), was renamed SEMO-1 (SELENBP1 ortholog with methanethiol oxidase activity). Worms rendered deficient in SEMO-1 not only showed decreased hydrogen sulfide production from methanethiol catabolism but they were also more resistant to oxidative stress and had an elevated life span. In contrast, resistance to selenite was significantly lowered in SEMO-1-deficient worms. Naturally occurring mutations of human SELENBP1 were introduced to recombinant SEMO-1 through site-directed mutagenesis and resulted in loss of its MTO activity, indicating a similar enzymatic mechanism for SELENBP1 and SEMO-1. In summary, SEMO-1 confers resistance to toxic selenite and the ability to metabolize toxic methanethiol. These beneficial effects might be a trade-off for its negative impact on C. elegans life span.