Curtis, Brian et al. (2021) International Worm Meeting "Identification of Novel Uric Acid Gluconucleosides in C. elegans regulated by insulin signaling"

Nelson, Hosea, Artyukhin, Alexander, Kim, Lee Joon, Le, Henry, Schroeder, Frank, Wrobel, Chester, Hu, Patrick, Burch, Jessica, Smith, Rubin, Curtis, Brian

[International Worm Meeting, 2021]

Few nucleoside-derived natural products have been identified from animals, despite the ubiquity of nucleosides in living organisms. Our recent metabolomic analyses of C. elegans revealed a variety of novel nucleoside derivatives, some of which incorporate additional moieties, for example ascarosides. Using a combination of chemical synthesis and the emerging electron microscopy technique microcrystal electron diffraction (MicroED) we elucidated the structures of two unusual uric acid nucleosides named uglas#1 and uglas#11, which are based on attachment of the purine base to glucose instead of ribose as in canonical nucleosides. These noncanonical gluconucleosides integrate the ascaroside pheromone ascr#1 as a building block. Via comparative metabolomics we showed that an enzyme from the carboxylesterase (CEST) family, CEST-1.1, is specifically required for the production of uglas#1 and its phosphorylated derivative, uglas#11, but not for the biosynthesis of structural isomers or other related gluconucleosides. Biosynthesis of the phosphorylated uglas#11 is starkly upregulated in long-lived daf-2 (e1368) mutants, suggesting a possible intersection of nucleoside metabolism and insulin signaling. The highly specific biosynthesis of uglas#1 and uglas#11 and their regulation by insulin signaling suggests that gluconucleosides may represent a novel class of signaling molecules.

Maaike C. W. van den Berg et al. (2006) European Worm Meeting "Sex-Dependent Resistance to the Fungal Pathogen Cryptococcus neoformans"

Maaike C. W. van den Berg, Jessica Z. Woerlee, Robin C. May, Hansong Ma

[European Worm Meeting, 2006]

Maaike C. W. van den Berg1,2, Jessica Z. Woerlee2, Hansong Ma1,2 & Robin C. May1. Cryptococcus neoformans is the causative agent of cryptococcosis, a fatal fungal disease of immunocompromised patients. Our group and others have made use of C. elegans as an alternative host for Cryptococcus, in order to investigate the molecular basis of host-pathogen interactions. Using this system, we now report that male C. elegans show greater resistance to killing by Cryptococcus than hermaphrodite animals and that this resistance can be induced in hermaphrodite animals by inappropriate activation of the male sex-determination pathway. Resistance is molecularly determined, rather than resulting from behavioural changes or reproductive differences, and requires the activity of the stress-response transcription factor DAF-16. Finally, we demonstrate that resistance to Cryptococcus neoformans correlates broadly with longevity within the Caenorhabditis genus. Our results suggest that many of the molecular determinants of longevity and immunity are the same and that differential regulation of these determinants may underlie much sex-dependent and species-dependent variation.