it is highly pathogenic and unsurpassed in its ability to develop resistance to every anthelmintic used in its control. Notably, these include a number of core drugs used for mass drug administration programs in humans. Anthelmintic resistance in H. contortus and related strongylids now threatens the viability of the sheep indus STI571 try throughout the world. This represents both a warn ing and a useful model for the consequences of the widespread intensive use of anthelmintics that are now being used to control human parasites in the developing world. H. contortus has a direct and rapid lifecycle. adults reside and mate in the abomasum of the ruminant host, then females produce eggs to be excreted in the feces.

The eggs embryonate, develop and hatch as first stage larvae, develop and molt to become second stage larvae, then molt again to become third stage larvae in Inhibitors,Modulators,Libraries the feces. The L3 migrate onto pasture to be ingested by the grazing ruminant host. The L3 shed the retained L2 cuticle in the rumen, travel to the abomasum and develop through to the fourth larval stage then adults in two to three weeks. As voracious blood feeders, H. contortus L4 and adults can cause severe hemorrhagic gastritis, hypo proteinemia, anemia and edema, with acute infections resulting in death of the animal host. One adult female can produce up to 10,000 eggs per day and a single animal can harbor thousands of worms. This extremely high fecundity, under conducive host and environmental conditions, can give rise to population explosions and devastating disease outbreaks.

Development occurs most rapidly in warm humid Inhibitors,Modulators,Libraries conditions, but the L4 stage can undergo arrested development Inhibitors,Modulators,Libraries within the host to survive adverse conditions such as prolonged drought or cold winters. This feature of facultative arrested develop ment, aided by movement of domestic livestock and climate change, has ensured the worldwide distribution and success of this parasite Inhibitors,Modulators,Libraries even though its evolutionary origins were in sub Saharan Africa. One striking feature of H. contortus, in common with related nematode species, is the extremely high level of genetic diversity that has been reported in both labora tory and field populations. this is thought to be predo minantly a function of its large effective population size. Genetic variation may underlie both the para sites remarkable ability to adapt to different climatic regions and host species and its alarming propen sity to develop drug resistance.

This high level of genetic polymorphism has also provided a major challenge to genome assembly, necessitating the production of an inbred line from which to prepare DNA template. In this paper, Inhibitors,Modulators,Libraries we describe the assembly and annotation of the draft genome of MHco3. N1, a genetically EPZ-5676 solubility well characterized inbred H. contortus strain that is susceptible to all major anthelmintic drugs.