Nature Genetics · 2015 · 135 citations · 80 references
Veterinary MedicineInfectious DiseasesMolecular GeneticsGenomicsHost-pathogen InteractionsTranscriptomicsHelminth InfectionsHelminth PathogenesisParasitic Disease PathogenesisParasitic PathogenesisZoonotic HelminthsZoonotic Parasitic DiseasesEarly Life InfectionHookworm ZoonosesMolecular Mechanisms Of InfectionPathogenesis Of Hookworm DiseaseProtein Family AnalysisWhole-genome Sequencing AnalysisZoonotic Pathogen CharacterizationZoonotic Pathogen Genomics
Erich Schwarz and colleagues report whole-genome sequencing of the zoonotic hookworm Ancylostoma ceylanicum. They also analyze the transcriptome through the course of infection in golden hamsters and identify groups of genes showing differential regulation across different stages. Hookworms infect over 400 million people, stunting and impoverishing them1,2,3. Sequencing hookworm genomes and finding which genes they express during infection should help in devising new drugs or vaccines against hookworms4,5. Unlike other hookworms, Ancylostoma ceylanicum infects both humans and other mammals, providing a laboratory model for hookworm disease6,7. We determined an A. ceylanicum genome sequence of 313 Mb, with transcriptomic data throughout infection showing expression of 30,738 genes. Approximately 900 genes were upregulated during early infection in vivo, including ASPRs, a cryptic subfamily of activation-associated secreted proteins (ASPs)8. Genes downregulated during early infection included ion channels and G protein–coupled receptors; this downregulation was observed in both parasitic and free-living nematodes. Later, at the onset of heavy blood feeding, C-lectin genes were upregulated along with genes for secreted clade V proteins (SCVPs), encoding a previously undescribed protein family. These findings provide new drug and vaccine targets and should help elucidate hookworm pathogenesis.
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