Poster Presentation 10th Australian Peptide Conference 2013

A Proteomic Analysis of low molecular weight Excretory/Secretory components of the blood-feeding hookworm Ancylostoma caninum (#167)

Catherine Shepherd 1 , David Wilson 1 , Severine Navarro 1 , Jason Mulvenna 2 , Marcus Baumann 2 , Norelle Daly 1 , Alex Loukas 1
  1. Centre for Biodiscovery and Molecular Development of Therapeutics, James Cook University, Cairns, QLD, Australia
  2. QMIR, ueensland Institute of Medical Research, Brisbane, QLD, Australia
Hookworms secrete a barrage of Excretory/Secretory molecules (ES) into the mammalian host’s gut mucosa to assist in blood-feeding and evasion of the host’s immune response.  ES products of the hookworm, Ancylostoma caninum, are therefore of interest as a source of therapeutic molecules for treating inflammatory disorders [1]. To date, hookworm ES proteins >10 kDa have been characterized using proteomics techniques,[2] and have displayed efficacy in suppressing inflammation associated with mouse models of colitis[3]. Some of the ES proteins responsible for suppressing inflammation have been identified and shown to protect against chemical colitis[4]. Much of the amino acid content of hookworm ES products is associated with as yet characterized low molecular weight peptides that pass through 10 kDa cut-off membranes but this material has not yet been characterized at the molecular level. Small peptides and compounds of less than 10 kDa are capable of acting in roles as diverse as signal transduction, immunomodulation and hormone-driven processes. In this investigation we carried out a shotgun proteomic analysis of the low molecular weight ES products secreted by A. caninum and show that defined fractions separated by RP-HPLC protect mice against TNBS colitis. Future work will identify the protective moieties and produce them in synthetic form for further trials. We have shown that hookworm secreted peptides possess anti-inflammatory properties and reveals their potential as a source of novel therapeutic compounds.
  1. Navarro, S., I. Ferreira, and A. Loukas, The hookworm pharmacopoeia for inflammatory diseases. Int J Parasitol, 2013. 43(3-4): p. 225-31
  2. Mulvenna, J., et al., Proteomics analysis of the excretory/secretory component of the blood-feeding stage of the hookworm, Ancylostoma caninum. Mol Cell Proteomics, 2009. 8(1): p. 109-21.
  3. Ruyssers, N.E., et al., Therapeutic potential of helminth soluble proteins in TNBS-induced colitis in mice. Inflamm Bowel Dis, 2009. 15(4): p. 491-500.
  4. Ferreira, I., et al., Hookworm Excretory/Secretory Products Induce Interleukin-4 (IL-4)+ IL-10+ CD4+ T Cell Responses and Suppress Pathology in a Mouse Model of Colitis. Infect Immun, 2013. 81(6): p. 2104-11.