@article{a944e90d0ccb493db5b0cff4ec14bd37,
title = "Microbial byproducts determine reproductive fitness of free-living and parasitic nematodes",
abstract = "Trichuris nematodes reproduce within the microbiota-rich mammalian intestine and lay thousands of eggs daily, facilitating their sustained presence in the environment and hampering eradication efforts. Here, we show that bacterial byproducts facilitate the reproductive development of nematodes. First, we employed a pipeline using the well-characterized, free-living nematode C. elegans to identify microbial factors with conserved roles in nematode reproduction. 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. Additionally, Trichuris muris eggs displayed defective hatching in the presence of fabH- or eutN-deficient E. coli due to reduced arginine or elevated aldehydes, respectively. T. muris reared in gnotobiotic mice colonized with these E. coli mutants displayed morphological defects and failed to lay viable eggs. These findings indicate that microbial byproducts mediate evolutionarily conserved transkingdom interactions that impact the reproductive fitness of distantly related nematodes.",
keywords = "C. elegans, E. coli, Trichuris, gut microbiome, helminths, nematode, transkingdom interactions",
author = "Mericien Venzon and Ritika Das and Luciano, {Daniel J.} and Julia Burnett and Park, {Hyun Shin} and Devlin, {Joseph Cooper} and Kool, {Eric T.} and Belasco, {Joel G.} and Hubbard, {E. Jane Albert} and Ken Cadwell",
note = "Funding Information: We wish to thank D. Jones, R. Rose, and L. Ash from the NYULH Metabolomics Laboratory (SCR_017935) and C. Yun, S. Cook, and D. Kahler from the High Throughput Biology Core (now Microscopy Laboratory, NIH S10 RR023704) for their help in acquiring and analyzing the data presented. Both Core Laboratories are funded partially by NIH/NCI P30CA016087. Some strains were built using strains provided by the CGC which is funded by the NIH Office Research Infrastructure Programs (P40 OD010440), and we thank WormBase. We also thank H. Darwin and M. Pacold for advice on microbial metabolism; S. Marion, C. Linton, M. Xu, A. Niranjan, D. Stokes, M. Lopez-Redondo, I. Irnov, V. Torres, S. Dyzenhaus, M. Hui, J. Richards (NYU), and E. Tait-Wojno (Univ. of Washington) for technical assistance and reagents; members of the Hubbard Lab, Cadwell Lab, and NYU Medical Scientist Training Program for constructive comments and technical assistance; and M. Alva, J. Carrasquillo, and D. Basnight for assistance with gnotobiotics. Funding: NIH grant DK093668 (K.C.), NIH grant AI121244 (K.C.), NIH grant HL123340 (K.C.), NIH grant AI130945 (K.C.), NIH grant AI140754 (K.C.), NIH grant DK124336 (K.C.), NIH grant R01GM130152 (E.J.A.H.), NIH grant R35GM134876 (E.J.A.H.), NIH grant R01GM035769 (J.G.B.), NIH grant 5T32AI100853 (M.V.), NIH grant T32GM136573 (M.V.), NIH grant T32GM007308 (M.V.), Faculty Scholar grant from the Howard Hughes Medical Institute (K.C.), Crohn's & Colitis Foundation (K.C.), Kenneth Rainin Foundation (K.C.), Judith & Stewart Colton Center of Autoimmunity (K.C.), and US National Cancer Institute (CA217809) (E.T.K.). K.C. is a Burroughs Wellcome Fund Investigator in the Pathogenesis of Infectious Diseases. M.V. R.D. E.J.A.H. and K.C. conceived the study and designed the experiments. M.V. R.D. and J.B. performed, analyzed, and interpreted all the experiments for T. muris and C. elegans. D.J.L. performed the bacterial cloning. H.S.P. and E.T.K. provided DarkZone and technical advice. J.C.D. provided technical assistance and advice for RNA-seq and analysis. K.C. E.J.A.H. and J.G.B. oversaw analysis and interpretation of all experiments described. M.V. R.D. E.J.A.H. and K.C. wrote the manuscript with inputs from all authors. 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. Funding Information: We wish to thank D. Jones, R. Rose, and L. Ash from the NYULH Metabolomics Laboratory (SCR_017935) and C. Yun, S. Cook, and D. Kahler from the High Throughput Biology Core (now Microscopy Laboratory, NIH S10 RR023704) for their help in acquiring and analyzing the data presented. Both Core Laboratories are funded partially by NIH/ NCI P30CA016087 . Some strains were built using strains provided by the CGC which is funded by the NIH Office Research Infrastructure Programs ( P40 OD010440 ), and we thank WormBase. We also thank H. Darwin and M. Pacold for advice on microbial metabolism; S. Marion, C. Linton, M. Xu, A. Niranjan, D. Stokes, M. Lopez-Redondo, I. Irnov, V. Torres, S. Dyzenhaus, M. Hui, J. Richards (NYU), and E. Tait-Wojno (Univ. of Washington) for technical assistance and reagents; members of the Hubbard Lab, Cadwell Lab, and NYU Medical Scientist Training Program for constructive comments and technical assistance; and M. Alva, J. Carrasquillo, and D. Basnight for assistance with gnotobiotics. Funding Information: Funding: NIH grant DK093668 (K.C.), NIH grant AI121244 (K.C.), NIH grant HL123340 (K.C.), NIH grant AI130945 (K.C.), NIH grant AI140754 (K.C.), NIH grant DK124336 (K.C.), NIH grant R01GM130152 (E.J.A.H.), NIH grant R35GM134876 (E.J.A.H.), NIH grant R01GM035769 (J.G.B.), NIH grant 5T32AI100853 (M.V.), NIH grant T32GM136573 (M.V.), NIH grant T32GM007308 (M.V.), Faculty Scholar grant from the Howard Hughes Medical Institute (K.C.), Crohn{\textquoteright}s & Colitis Foundation (K.C.), Kenneth Rainin Foundation (K.C.), Judith & Stewart Colton Center of Autoimmunity (K.C.), and US National Cancer Institute ( CA217809 ) (E.T.K.). K.C. is a Burroughs Wellcome Fund Investigator in the Pathogenesis of Infectious Diseases. Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",
year = "2022",
month = jun,
day = "8",
doi = "10.1016/j.chom.2022.03.015",
language = "English",
volume = "30",
pages = "786--797.e8",
journal = "Cell Host and Microbe",
issn = "1931-3128",
publisher = "Cell Press",
number = "6",
}