From the egg stage through L2, the worms are present in the fecal pat. Upon developing to L3sh they become more motile and migrate from the pat to better position themselves for ingestion by the host. Of the 24 peptides involved in energy metabolism in the free living stages of development, 17 are as sociated with methane metabolism. As the free living stages of both species are found in the fecal pat and the fecal pat is a methane rich environment, this is not sur prising. Only one of the 24 peptides is up regulated in the L3sh and classified as an enzyme involved in oxidative phosphorylation rather than methane metabol ism. It is possible that this becomes more functional as the worm distances itself from the fecal pat and readies itself for ingestion by the host.
It is also interesting to speculate that environmental queues i. e. host GI tract, may down regulate transcriptional activity of the proteins involved Inhibitors,Modulators,Libraries in methane metabolism and in turn in duce exsheathment and worm development. In C. oncophora, the KEGG category metabolism of cofactors and vitamins was significantly more abundant in the parasitic stages than in the free living stages. The specific enzymes involved are associated with pantothenate and CoA biosynthesis, and thiamine metabolism. All three peptides were up regulated Inhibitors,Modulators,Libraries only in adult females. Inasmuch as these enzymes were not observed in abundance in fecal eggs, their functions are likely related specifically to females or to egg development in utero. While many of the transcripts were stage specific, others were expressed in all stages.
These constitutively expressed transcripts are likely involved in core molecu lar processes used to sustain life, as shown by the domains found within them. This conclusion is also bolstered by the embryonic lethal phenotypes predicted Cilengitide for the majority of the constitutively expressed trans cripts that link to an RNAi phenotype in C. elegans. These transcripts and their encoded proteins should make attractive drug targets provided sufficient variation can be found between parasite and host proteins. Conclusions Control of parasitic nematodes is routinely accomplished through anthelminthic drugs. Resistance to these drugs is increasingly Inhibitors,Modulators,Libraries becoming a problem especially in live stock hosts. To date, resistance has surfaced to nearly all commercially available drugs.
In an effort to better understand this resistance and help combat the higher Inhibitors,Modulators,Libraries production costs associated with the lack of efficacy, a detailed study of these parasites at a molecular level was conducted. To this end, we have generated comprehen sive data on the transcriptomes of all discernible life cycle stages of these two organisms. The genome sequences for C. oncophora and O. ostertagi have been initiated in an effort to complement and complete this work. The cDNA sequences generated in this study will enable bet ter annotation of these genomes upon completion.