Pathogens (Jan 2023)

Excretory/Secretory Proteome of Females and Males of the Hookworm <i>Ancylostoma ceylanicum</i>

  • Samuel C. Uzoechi,
  • Bruce A. Rosa,
  • Kumar Sachin Singh,
  • Young-Jun Choi,
  • Bethany K. Bracken,
  • Paul J. Brindley,
  • R. Reid Townsend,
  • Robert Sprung,
  • Bin Zhan,
  • Maria-Elena Bottazzi,
  • John M. Hawdon,
  • Yide Wong,
  • Alex Loukas,
  • Sergej Djuranovic,
  • Makedonka Mitreva

DOI
https://doi.org/10.3390/pathogens12010095
Journal volume & issue
Vol. 12, no. 1
p. 95

Abstract

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The dynamic host-parasite mechanisms underlying hookworm infection establishment and maintenance in mammalian hosts remain poorly understood but are primarily mediated by hookworm’s excretory/secretory products (ESPs), which have a wide spectrum of biological functions. We used ultra-high performance mass spectrometry to comprehensively profile and compare female and male ESPs from the zoonotic human hookworm Ancylostoma ceylanicum, which is a natural parasite of dogs, cats, and humans. We improved the genome annotation, decreasing the number of protein-coding genes by 49% while improving completeness from 92 to 96%. Compared to the previous genome annotation, we detected 11% and 10% more spectra in female and male ESPs, respectively, using this improved version, identifying a total of 795 ESPs (70% in both sexes, with the remaining sex-specific). Using functional databases (KEGG, GO and Interpro), common and sex-specific enriched functions were identified. Comparisons with the exclusively human-infective hookworm Necator americanus identified species-specific and conserved ESPs. This is the first study identifying ESPs from female and male A. ceylanicum. The findings provide a deeper understanding of hookworm protein functions that assure long-term host survival and facilitate future engineering of transgenic hookworms and analysis of regulatory elements mediating the high-level expression of ESPs. Furthermore, the findings expand the list of potential vaccine and diagnostic targets and identify biologics that can be explored for anti-inflammatory potential.

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