Ancylostoma secreted protein 2: cloning and characterization of a second member of a family of nematode secreted proteins from Ancylostoma caninum

Hawdon, John M.; Narasimhan, Sukanya; Hotez, Peter J.

doi:10.1016/s0166-6851(99)00011-0

Cited by 162 publications

(139 citation statements)

References 32 publications

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“…Developmental studies carried out with the dog hookworm, A. caninum, indicated that products secreted during larval invasion are likely involved in the transition to parasitism and infectivity (Hawdon et al, 1999). Helminth proteins implicated in the tissue invasion process are particularly good candidate antigens for the development of vaccines and drugs.…”

Section: Discussionmentioning

confidence: 99%

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Necator americanus: The Na-ASP-2 protein secreted by the infective larvae induces neutrophil recruitment in vivo and in vitro

Bower¹,

Constant²,

Méndez³

2008

Experimental Parasitology

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The L3-secreted Ancylostoma Secreted Protein-2 from the human hookworm Necator americanus (Na-ASP-2) has been selected as a candidate vaccine antigen in anticipation of clinical trials. Its crystal structure revealed that Na-ASP-2 has structural and charge similarities to CC-chemokines, suggesting that it might act as a chemokine mimic when released by the infective larvae during tissue migration. Using the air pouch model of acute inflammation, we found that Na-ASP-2 induced a significant leukocyte influx to the skin pouch, mostly comprised of neutrophils (60%) and monocytes (30%) that was transient and resolved in 24 h. Other hookworm larval proteins did not cause any inflammatory leukocytes to migrate into air pouches. In vitro chemotaxis assays confirmed our results and demonstrated that leukocyte migration was a direct effect of Na-ASP-2 exposure and not caused by other molecules released by host cells in the inflammatory microenvironment or by the expression vector.

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Section: Discussionmentioning

confidence: 99%

“…When L3 of the canine hookworm A. caninum are activated in vitro, they release metalloproteases (Hawdon et al, 1995) and other molecules of unknown function referred to as Ancylostoma Secreted Protein 1 and 2 (Ac-ASP-1, Ac-ASP-2; Hawdon et al, 1996;Hawdon et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Necator americanus: The Na-ASP-2 protein secreted by the infective larvae induces neutrophil recruitment in vivo and in vitro

Bower¹,

Constant²,

Méndez³

2008

Experimental Parasitology

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“…Most of these were highly transcribed in the L4 stage, whereas others were highly enriched in the adult male worms. The latter was especially the case for the N-type single-domain ASPs Oo-ASP1 and Oo-ASP2 and also for Oo-ASP3, which is a homologue of the H. contortus and A. caninum C-type single-domain Hc24 and ASP 2 (Schallig et al, 1997b;Hawdon et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

“…Both Hc24 and Oo-ASP3 were most abundant in adult worms and were both localised in the pharyngeal region (Schallig et al, 1997b), which could indicate a conserved function. Hawdon et al (1999) also demonstrated transcription of A. caninum ASP2 in adult worms but protein expression in the different stages or localisation was not evaluated. More sequence variation was seen for the two-domain ASP molecules, suggesting a higher selection pressure on these genes.…”

Section: Discussionmentioning

confidence: 99%

Gender-enriched transcription of activation associated secreted proteins in Ostertagia ostertagi

Visser

Zeveren

Meyvis

et al. 2008

International Journal for Parasitology

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Activation associated secreted proteins (ASP) are members of a nematode-specific protein family belonging to the SCP/Tpx-1/Ag5/ PR-1/Sc7 family. Three different types of molecules have been identified in this family: two-domain ASPs and single-domain ASPs showing homology to either the C-terminal or N-terminal domain of the two-domain ASP. The function of these proteins is still unclear, but a role in transition to parasitism and a role as allergen are often suggested. Here we report that the abomasal cattle parasite Ostertagia ostertagi produces at least 15 ASPs, including two-domain and C-and N-type single-domain ASPs. Ten of these are highly transcribed in the L4 stage, whereas others are highly enriched in adult male worms. The latter was especially the case for the N-type single-domain ASPs Oo-ASP1 and Oo-ASP2 and also for Oo-ASP3, which is homologous with the Haemonchus contortus and Ancylostoma caninum Ctype single-domain ASPs. Immunohistochemistry showed that Oo-ASP3 was localised in the oesophagus. Oo-ASP1 and Oo-ASP2 on the other hand were localised in the reproductive tract of both male and female worms, suggesting a role in reproduction or in the development of the reproductive tract. Ó

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“…Ancylostoma Secreted Proteins, ASP-1 and ASP-2 [3,4] and several hookworm digestive proteases like aspartic haemoglobinase [5] are being studied as potential vaccines against hookworm infections. In addition, hookworm gene products may have application against other diseases.…”

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confidence: 99%

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

Abubucker

Martin

Yin

et al. 2008

Molecular and Biochemical Parasitology

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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 5,538 genes in the GSS assembly, for a total of 9,113 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. Keywordshookworm; Ancylostoma caninum; genome survey sequences; expressed sequence tags; genome; comparative genomics Hookworms are parasitic nematodes that live in the host small intestine and affect mammals including humans, dogs, and cats. Ancylostoma duodenale and Necator americanus infect close to a billion people [1] causing anemia and malnutrition, and also diminished physical and cognitive development in children. A. caninum is a hookworm species that infects canids and is commonly used as a model for studying human infections. Hookworm infections are usually *Corresponding Author: Tel: +1-314-2861118; Fax: +1-314-2861810, E-mail address: mmitreva@watson.wustl.edu (M. Mitreva). Note: Nucleotide sequences data reported in this paper are available in the GenBank, EMBL and DDBJ databases under the accession numbers CW698017 -CW717115, CW958972 -CW978588, CZ194948 -CZ250652.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. , our recent genome size estimate using flow sorted nuclei surprisingly revealed a genome more than six times this size. Genome size was estimated by prodidium iodide staining and flow cytometry of isolated nuclei following methods described in [10]. To prepare the nuclei, the A. caninum L3s were washed in cold Galbraith buffer pH 7.2 and then pipetted into a plastic petri dish along with 30-50 μl cold Galbraith buffer and chopped (50 times) with a fresh single edge razor blade. The chopped material was washed into one edge of the (tilted) petri dish using an additional 1 ml of cold Galbraith buffer (per liter: 4.26g MgCl2, 8.84 g sodium citrate, 4.2 g [N-morpholino] propane sulfonic acid, 1m...

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Ancylostoma secreted protein 2: cloning and characterization of a second member of a family of nematode secreted proteins from Ancylostoma caninum

Cited by 162 publications

References 32 publications

Necator americanus: The Na-ASP-2 protein secreted by the infective larvae induces neutrophil recruitment in vivo and in vitro

Necator americanus: The Na-ASP-2 protein secreted by the infective larvae induces neutrophil recruitment in vivo and in vitro

Gender-enriched transcription of activation associated secreted proteins in Ostertagia ostertagi

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

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