The genome and transcriptome of Haemonchus contortus, a key model parasite for drug and vaccine discovery

被引:302
作者
Laing, Roz [1 ]
Kikuchi, Taisei [2 ,3 ]
Martinelli, Axel [2 ]
Tsai, Isheng J. [2 ,3 ]
Beech, Robin N. [4 ]
Redman, Elizabeth [5 ]
Holroyd, Nancy [2 ]
Bartley, David J. [6 ]
Beasley, Helen [2 ]
Britton, Collette [1 ]
Curran, David [7 ]
Devaney, Eileen [1 ]
Gilabert, Aude [7 ]
Hunt, Martin [2 ]
Jackson, Frank [6 ]
Johnston, Stephanie L. [1 ]
Kryukov, Ivan [7 ]
Li, Keyu [7 ]
Morrison, Alison A. [6 ]
Reid, Adam J. [2 ]
Sargison, Neil [8 ]
Saunders, Gary I. [1 ,2 ]
Wasmuth, James D. [7 ]
Wolstenholme, Adrian [9 ,10 ]
Berriman, Matthew [2 ]
Gilleard, John S. [5 ]
Cotton, James A. [2 ]
机构
[1] Univ Glasgow, Coll Med Vet & Life Sci, Inst Infect Immun & Inflammat, Glasgow G61 1QH, Lanark, Scotland
[2] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England
[3] Miyazaki Univ, Fac Med, Dept Infect Dis, Div Parasitol, Miyazaki 8891692, Japan
[4] McGill Univ, Inst Parasitol, Ste Anne De Bellevue, PQ H9X 3V9, Canada
[5] Fac Vet Med, Dept Comparat Biol & Expt Med, Calgary, AB T2N 1N4, Canada
[6] Moredun Res Inst, Penicuik EH26 0PZ, Midlothian, Scotland
[7] Fac Vet Med, Dept Ecosyst & Publ Hlth, Calgary, AB T2N 1N4, Canada
[8] Univ Edinburgh, Royal Dick Sch Vet Studies, Easter Bush Vet Ctr, Roslin EH25 9RG, Midlothian, Scotland
[9] Univ Georgia, Dept Infect Dis, Athens, GA 30602 USA
[10] Univ Georgia, Ctr Trop & Emerging Global Dis, Athens, GA 30602 USA
基金
英国生物技术与生命科学研究理事会; 加拿大自然科学与工程研究理事会; 英国惠康基金; 加拿大健康研究院;
关键词
NEMATODE CAENORHABDITIS-ELEGANS; CYSTEINE PROTEASES; ANTHELMINTIC RESISTANCE; GENE-EXPRESSION; FUNCTIONAL RECONSTITUTION; BLOOD-LOSS; MEMBRANE; SEQUENCE; GUT; FAMILY;
D O I
10.1186/gb-2013-14-8-r88
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 [微生物学]; 090105 [作物生产系统与生态工程];
摘要
Background: The small ruminant parasite Haemonchus contortus is the most widely used parasitic nematode in drug discovery, vaccine development and anthelmintic resistance research. Its remarkable propensity to develop resistance threatens the viability of the sheep industry in many regions of the world and provides a cautionary example of the effect of mass drug administration to control parasitic nematodes. Its phylogenetic position makes it particularly well placed for comparison with the free-living nematode Caenorhabditis elegans and the most economically important parasites of livestock and humans. Results: Here we report the detailed analysis of a draft genome assembly and extensive transcriptomic dataset for H. contortus. This represents the first genome to be published for a strongylid nematode and the most extensive transcriptomic dataset for any parasitic nematode reported to date. We show a general pattern of conservation of genome structure and gene content between H. contortus and C. elegans, but also a dramatic expansion of important parasite gene families. We identify genes involved in parasite-specific pathways such as blood feeding, neurological function, and drug metabolism. In particular, we describe complete gene repertoires for known drug target families, providing the most comprehensive understanding yet of the action of several important anthelmintics. Also, we identify a set of genes enriched in the parasitic stages of the lifecycle and the parasite gut that provide a rich source of vaccine and drug target candidates. Conclusions: The H. contortus genome and transcriptome provide an essential platform for postgenomic research in this and other important strongylid parasites.
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