Belasco, Joel G., Cadwell, Ken, Luciano, Daniel J., Das, Ritika, Venzon, Mericien, Hubbard, E. Jane Albert
[
International Worm Meeting,
2021]
Parasitic nematodes infect over one billion people worldwide and although the majority of them live in the digestive tract, a possible role for the microbiota in determining successful host infection is underexplored. The Trichuris nematode parasite lives in the microbiota-rich mammalian cecum for years, and it has an enormous reproductive capacity that contributes to its infectious spread. We previously determined that C. elegans germline development is sensitive to the microbial environment. Though the two nematode species are not closely related, we predicted that some aspects of reproduction in the well-characterized, model organism C. elegans may be conserved in Trichuris. To assess systematically which components of the bacterial diet are most important for C. elegans reproduction, we screened an E. coli library for mutants that, when fed to C. elegans, interfered with timely fertility. We identified ten E. coli mutants. Focusing on two that function in fatty acid biosynthesis (fabF, fabH) and two that function in ethanolamine utilization (eutD, eutN), we found that fabF and eutN delayed C. elegans germline development relative to somatic development, though none of the four reduced germline progenitor numbers and none were dependent upon DAF-2 insulin or DAF-7 TGFB signaling pathways. Metabolomics and functional analysis unexpectedly revealed that fabH E. coli mutants provide insufficient arginine, such that arginine supplementation rescued the C. elegans fertility delay. We further investigated whether E. coli mutants might interfere with development or reproduction of the Trichuris species that infects mice, Trichuris muris. Remarkably, fabH and eutN mutant E. coli were associated with T. muris hatching defects, the former also being arginine-dependent, while eutN likely acts by producing a toxic substance. Both were also associated with aberrant reproduction of T. muris in vivo. Overall, these findings establish C. elegans as a novel system for investigating the effects of specific microbial genes and pathways in supporting the parasitic nematode life cycle.