Dataset Information

The canine hookworm genome: analysis and classification of Ancylostoma caninum survey sequences.

ABSTRACT: Hookworms infect nearly a billion people. The Ancylostoma caninum hookworm of canids is a model for studying human infections and information from its genome coupled with functional genomics and proteomics can accelerate progress towards hookworm control. As a step towards a full-scale A. caninum genome project, we generated 104,000 genome survey sequences (GSSs) and determined the genome size of the canine hookworm. GSSs assembled into 57.6 Mb of unique sequence from a genome that we estimate by flow cytometry of isolated nuclei to be 347 +/- 1.2 Mb, substantially larger than other Rhabditina species. Gene finding identified 5538 genes in the GSS assembly, for a total of 9113 non-redundant A. caninum genes when EST sequences are also considered. Functional classifications of many of the 70% of genes with homology to genes in other species are provided based on gene ontology and KEGG associations and secreted and membrane-bound proteins are also identified.

SUBMITTER: Abubucker S

PROVIDER: S-EPMC2265417 | biostudies-literature | 2008 Feb

REPOSITORIES: biostudies-literature

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The canine hookworm genome: analysis and classification of Ancylostoma caninum survey sequences.

Abubucker Sahar S Martin John J Yin Yong Y Fulton Lucinda L Yang Shiaw-Pyng SP Hallsworth-Pepin Kym K Johnston J Spencer JS Hawdon John J McCarter James P JP Wilson Richard K RK Mitreva Makedonka M

Molecular and biochemical parasitology 20071109 2

Hookworms infect nearly a billion people. The Ancylostoma caninum hookworm of canids is a model for studying human infections and information from its genome coupled with functional genomics and proteomics can accelerate progress towards hookworm control. As a step towards a full-scale A. caninum genome project, we generated 104,000 genome survey sequences (GSSs) and determined the genome size of the canine hookworm. GSSs assembled into 57.6 Mb of unique sequence from a genome that we estimate b ...[more]

PMID: 18082904

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Project description:BACKGROUND:The canine hookworm, Ancylostoma caninum is the most prevalent and important intestinal nematode parasite of dogs in the USA. Hookworms are typically well controlled by treatment with all commonly used anthelmintics that are approved for this use in dogs. However, in the past few years, cases of recurrent/persistent canine hookworm infections appear to have dramatically increased, suggesting that anthelmintic resistance (AR) may have evolved in this parasite. These cases are highly overrepresented by greyhounds, but multiple other breeds are also represented. The aim of this study was to characterize several of these suspected resistant isolates using in vitro, genetic and clinical testing to determine if these cases represent true anthelmintic resistance in A. caninum. METHODS:Fecal samples containing hookworm eggs from three cases of persistent hookworm infections; one from a greyhound, one from a miniature schnauzer and one from a hound-mix, were received by our laboratory. These were then used to establish infections in laboratory dogs and to perform egg hatch assays (EHA) and larval development assays (LDA) for detecting resistance to benzimidazoles and macrocyclic lactones, respectively. Additional EHA and LDA were performed on eggs recovered from the laboratory-induced infections. Fecal egg count reduction tests were performed to detect resistance to pyrantel. Deep amplicon sequencing assays were developed to measure the frequency of non-synonymous single nucleotide polymorphisms (SNP) at codons 167, 198 and 200 of the A. caninum isotype-1 β-tubulin gene. RESULTS:Resistance ratios for the three A. caninum isolates tested ranged from 6.0 to > 100 and 5.5 to 69.8 for the EHA and LDA, respectively. Following treatment with pyrantel, reduction in faecal egg counts was negative or 0%. Deep amplicon sequencing of the isotype-1 β-tubulin gene identified a high frequency of resistance-associated SNPs at codon 167 in all three resistant isolates and in two additional clinical cases. CONCLUSIONS:These data conclusively demonstrate multiple anthelmintic resistance in multiple independent isolates of A. caninum, strongly suggesting that this is an emerging problem in the USA. Furthermore, evidence suggest that these resistant hookworms originate from racing greyhound farms and kennels, though additional research is needed to confirm this.

Project description:Soil-transmitted nematodes infect over a billion people and place several billion more at risk of infection. Hookworm disease is the most significant of these soil-transmitted nematodes, with over 500 million people infected. Hookworm infection can result in debilitating and sometimes fatal iron-deficiency anemia, which is particularly devastating in children and pregnant women. Currently, hookworms and other soil-transmitted nematodes are controlled by administration of a single dose of a benzimidazole to targeted populations in endemic areas. While effective, people are quickly re-infected, necessitating frequent treatment. Widespread exposure to anthelmintic drugs can place significant selective pressure on parasitic nematodes to generate resistance, which has severely compromised benzimidazole anthelmintics for control of livestock nematodes in many areas of the world. Here we report, to our knowledge, the first naturally occurring multidrug-resistant strain of the canine hookworm Ancylostoma caninum. We reveal that this isolate is resistant to fenbendazole at the clinical dosage of 50 mg/kg for 3 days. Our data shows that this strain harbors a fixed, single base pair mutation at amino acid 167 of the β-tubulin isotype 1 gene, and by using CRISPR/Cas9 we demonstrate that introduction of this mutation into the corresponding amino acid in the orthologous β-tubulin gene of Caenorhabditis elegans confers a similar level of resistance to thiabendazole. We also show that the isolate is resistant to the macrocyclic lactone anthelmintic ivermectin. Understanding the mechanism of anthelmintic resistance is important for rational design of control strategies to maintain the usefulness of current drugs, and to monitor the emergence of resistance. The isolate we describe represents the first multidrug-resistant strain of A. caninum reported, and our data reveal a resistance marker that can emerge naturally in response to heavy anthelminthic treatment.

Dataset Information

The canine hookworm genome: analysis and classification of Ancylostoma caninum survey sequences.

Publications

The canine hookworm genome: analysis and classification of Ancylostoma caninum survey sequences.

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