Summary
A distinguishing feature of Trichuris nematodes is that these parasitic worms reproduce within the digestive tracts of humans and other mammalian hosts shedding thousands of eggs daily, facilitating their sustained presence in the environment and hampering eradication efforts. Although this aspect of the lifecycle places Trichuris in a microbiota-rich environment, metabolic byproducts of bacteria that facilitate the reproductive development of parasites are unknown. Here, we employ a pipeline using the well-characterized free-living nematode C. elegans to identify microbial factors with conserved roles in the reproduction of nematodes. A screen for E. coli mutants that impair C. elegans fertility identified genes in fatty acid biosynthesis and ethanolamine utilization pathways, including fabH and eutN. Trichuris muris eggs displayed defective hatching in the presence of E. coli deficient in fabH or eutN due to reduction in arginine or elevated levels of aldehydes, respectively. Remarkably, T. muris reared in gnotobiotic mice colonized with these E. coli mutants displayed profound abnormalities including morphological defects and a failure to lay viable eggs. These findings indicate that microbial byproducts mediate evolutionarily conserved transkingdom interactions that impact the reproductive fitness of distantly-related nematodes.
Competing Interest Statement
K.C. has received research support from Pfizer, Takeda, Pacific Biosciences, Genentech, and Abbvie. K.C. has consulted for or received honoraria from Puretech Health, Genentech, and Abbvie. K.C. holds U.S. patent 10,722,600 and provisional patent 62/935,035 and 63/157,225, and E.J.A.H. holds US patent 6,087,153.
Footnotes
We now include transcriptomes of individual parasitic worms from mice monocolonized with mutant E. coli and an accompanying computational analysis that compares these results with the transcriptional program during C. elegans development. Data from additional experiments have also been included in the supplemental figures. Two co-authors have been added in recognition of their contributions to this revised manuscript.
