Xenobiotic detoxification in the nematode Caenorhabditis elegans

Abstract

The nematode Caenorhabditis elegans is an important model organism for the study of such diverse aspects of animal physiology and behavior as embryonic development, chemoreception, and the genetic control of lifespan. Yet, even though the entire genome sequence of this organism was deposited into public databases several years ago, little is known about xenobiotic metabolism in C. elegans. In part, the paucity of detoxification information may be due to the plush life enjoyed by nematodes raised in the laboratory. In the wild, however, these animals experience a much greater array of chemical assaults. Living in the interstitial water of the soil, populations of C. elegans exhibit a boom and bust lifestyle characterized by prodigious predation of soil microbes punctuated by periods of dispersal as a non-developing alternative larval stage. During the booming periods of population expansion, these animals almost indiscriminately consume everything in their environment including any number of compounds from other animals, microorganisms, plants, and xenobiotics. Several recent studies have identified many genes encoding sensors and enzymes these nematodes may use in their xeno-coping strategies. Here, we will discuss these recent advances, as well as the efforts by our lab and others to utilize the genomic resources of the C. elegans system to elucidate this nematode's molecular defenses against toxins.

Comparative transcriptomics of two pathogenic pinewood nematodes yields insights into parasitic adaptation to life on pine hosts

“…We checked the enzymes in these pathways and found that the enzymes that participate in these metabolism pathways were mainly cytochromes P450 (CYPs), glutathione S-transferases (GSTs), short-chain dehydrogenases/reductases (SDRs), UDP-glucuronosyl transferases family members (UGTs) and some others (Table 4, Supplemental Tables S4 and S5). The result is similar to that found in C. elegans (Lindblom and Dodd, 2006).…”

“…They are important enzymes in xenobiotic metabolism of nematodes (Lindblom and Dodd, 2006). There were 48 and 62 transcripts of CYP450 that were found in B. xylophilus and B. mucronatus, respectively.…”

Indoles from commensal bacteria extend healthspan

“…To identify genes mediating the effects of indoles on healthspan, we assessed the effects of indoles on loss-of-function alleles in genes known to mediate conditioning, regulate lifespan, or modulate stress responses in C. elegans (11,13,21). These included the FOXO homolog DAF-16, the insulin receptor homolog DAF-2, the sirtuin homolog SIR2.1, the Nrf-2 homolog SKN-1, the dopamine receptor DOP-3, the tyrosine hydroxylase CAT-2, and AHR-1 (22), which encodes an ortholog of the mammalian AHR, a xenobiotic receptor that can bind to a variety of small molecules including indole (23). Similar to N2, shift in the survival curves was still evident with K12 compared with K12ΔtnaA in daf-16(m26), daf-2(e1370), sir2.1(ok434), skn-1(zu169), dop-3 (vs.106), and cat-2(e1112) animals (Fig.…”

Genome sequence of the metazoan plant-parasitic nematode Meloidogyne incognita

“…More striking still was the reduction in glutathione S-transferases (GSTs) and cytochromes P450 (CYPs), enzymes involved in xenobiotic metabolism and protection against peroxidative damage. Whereas C. elegans has 44 GSTs, including representatives from the Omega, Sigma and Zeta classes 23 Table 18).…”