How Zinc Transporters in Escherichia coli Influence Ageing in the Nematode Caenorhabditis elegans

Abstract

Gut microbes play an important role in mammalian physiology. Escherichia coli not only provide the Caenorhabditis elegans with vital nutrients but also influence worms lifespan. Studying such interactions could help us to understand how intestinal microbes influence mammalian ageing. A recent gene deletion study of 1041 E. coli in our lab identified 9 genes that are involved in the increase of worm’s lifespan. One gene identified was ZnuB, which forms part of the high affinity znuABC zinc ABC transporters, plays an important role in zinc homeostasis, and has been suggested to play a role in increased lifespan. To validate this hypothesis, levels of zinc were measured using ICP-MS in znuA, znuB, and znuC mutant bacteria and worms fed with the mutants, and compared with zinc levels in WT bacteria and C. elegans fed with WT bacteria. Zinc levels were also measured in LB and NGM media.
It was found that although bacteria and worms could obtain zinc from LB media, the level of zinc was lower in worms and the three mutant bacteria than in WT bacteria alone. Lifespan of worms fed with those mutants was investigated. Worms fed with znuB and znuC bacteria showed extended lifespan, compered to worms fed with znuA bacteria. Reduced fecundity was observed in experimental worms fed with mutant as compared to worms fed with WT bacteria. Moreover, the worms fed with the znuB showed a delay in the reproductive cycle. These results suggest that reducing zinc concentration itself in the mutant bacteria does not make the worms live longer, but the mutation in the znuB could produce different effects. Results of zinc supplement experiments using mutants showed reversal effect on worm developmental delay when fed with znuB and zinc supplements. These results show that the znuB not only plays an important role in zinc uptake by bacteria, but also affects the lifespan of C. elegans.