Role ofugtgenes in detoxification and glycosylation of 1-hydroxy phenazine (1-HP) inCaenorhabditis elegans

Abstract

Caenorhabditis elegansis an ideal model organism to study the xenobiotic detoxification pathways of various natural and synthetic toxins. One toxin shown to cause death inC. elegansis 1-hydroxyphenazine (1-HP), a molecule produced by the bacteriumPseudomonas aeruginosa.We previously showed that the median lethal dose (LD50) for 1-HP inC elegansis 179 μM in PD1074 and between 150-200 μM in N2 (C. eleganslab strain). We also showed thatC. elegansdetoxifies 1-HP by glycosylation by adding one, two, or three glucose molecules in N2 worms. This study tested whether UDP-glycosyltransferase (ugt)genes play a role in 1-HP detoxification. We show thatugt-23andugt-49 knockout mutants are more sensitive to 1-HP. Our data also show thatugt-23knockout mutants produce reduced amounts of the trisaccharide sugars, while theugt-49knockout mutants produce reduced amounts of all 1-HP derivatives except for the glucopyranosyl product. We have also characterized the structure of the trisaccharide sugar phenazine structures made byC. elegansand show that one of the sugar modifications contains an N-acetylglucosamine (GlcNAc) in place of glucose. This implies broad specificity regarding UGT function and the role of genes other thanogt-1in adding GlcNAc, at least in small-molecule detoxification.