Genome of the human hookworm Necator americanus

Abstract

The hookworm Necator americanus is the predominant soil-transmitted human parasite. Adult worms feed on blood in the small intestine, causing iron deficiency anaemia, malnutrition, growth and development stunting in children, and severe morbidity and mortality during pregnancy in women. Characterization of the first hookworm genome sequence (244 Mb, 19,151 genes) identified genes orchestrating the hookworm's invasion of the human host, genes involved in blood feeding and development, and genes encoding proteins that represent new potential drug targets against hookworms. N. americanus has undergone a considerable and unique expansion of immunomodulator proteins, some of which we highlight as potential novel treatments against inflammatory diseases. We also utilize a protein microarray to demonstrate a post-genomic application of the hookworm genome sequence. This genome provides an invaluable resource to boost ongoing efforts towards fundamental and applied post-genomic research, including the development of new methods to control hookworm and human immunological diseases.

Secreted Proteomes of Different Developmental Stages of the Gastrointestinal Nematode Nippostrongylus brasiliensis

“…Also, downstream analysis for transcript abundance estimation and differential expression between life stages was performed following the protocol described in (21). Reconstructed transcripts were annotated using the Trinotate pipeline (http://trinotate.sourceforge.net/), a blastx search against the NEMBASE4 (http://www.nematodes.org/nembase4/), and against the entire genome sequence of the human hookworm N. americanus (18) to confirm their origin and rule out contamination from host or bacterial sources. Proteins were then conceptually translated from the predicted coding domains of individual cDNA sequences.…”

“…Large-scale data comparisons between the secreted proteome from N. brasiliensis and available genomic and proteomic data for N. americanus were performed (18). This comprehensive analysis of the proteins and mRNAs produced by N. brasiliensis provides new insights into the molecular interactions at the host-parasite interface and highlight the molecular similarities between N. brasiliensis and N. americanus, emphasizing the utility of this model rodent nematode for exploring the immunobiology of hookworm infections, and as a model for the discovery and development of new therapeutic approaches to controlling gastrointestinal nematodes.…”

The barber's pole worm CAP protein superfamily — A basis for fundamental discovery and biotechnology advances

“…americanus (cf. Hawdon et al, 1996, 1999;Datu et al, 2008;Tang et al, 2014;Schwarz et al, 2015), but contrasts with the small numbers of homologous genes inferred from transcriptomic and genomic sequence data sets for some other nematodes studied to date, including Ascaris suum, Toxocara canis and Trichuris suis (see Jex et al, 2011Jex et al, , 2014Zhu et al, 2015). The reason(s) for this apparent difference is unclear, but could relate to differences in developmental and reproductive biology as well as varying modes of host invasion and immune modulation or evasion among nematode species (cf.…”

“…Although no direct comparison was undertaken here, this upregulation appears to be distinct from hookworms A. caninum, A. ceylanicum and N. americanus (see Goud et al, 2005;Datu et al, 2008;Osman 2012;Schwarz et al, 2015), which usually undergo percutaneous, pulmonary and/or somatic migration, and establish in the small intestine rather than the abomasum. This latter difference could explain the apparent expansions of CAP protein genes in N. americanus (n = 128; Tang et al, 2014) and A. ceylanicum (n = 432; Schwarz et al, 2015) compared with H. contortus. The relatively high proportion (28%) of CAP molecules of H. contortus with homologues in C. elegans contrasts with the situation for N. americanus and A. ceylanicum (see Tang et al, 2014;Schwarz et al, 2015), in which only six of 137 (4.3%) CAP proteins have orthologues in the free-living nematode.…”

“…This latter difference could explain the apparent expansions of CAP protein genes in N. americanus (n = 128; Tang et al, 2014) and A. ceylanicum (n = 432; Schwarz et al, 2015) compared with H. contortus. The relatively high proportion (28%) of CAP molecules of H. contortus with homologues in C. elegans contrasts with the situation for N. americanus and A. ceylanicum (see Tang et al, 2014;Schwarz et al, 2015), in which only six of 137 (4.3%) CAP proteins have orthologues in the free-living nematode. In addition, there are five paralogs encoding related proteins in H. contortus, which further suggests that they relate to parasite-specific functions.…”