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

Abstract

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.

Document Details

Document Type
Pub Defense Publication
Publication Date
Jan 06, 2023
Source ID
10.3390/pathogens12010095

Entities

People

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

Organizations

  • Defense Advanced Research Projects Agency
  • Washington University in St. Louis

Tags

Fields of Study

  • Biology

Readers

  • Infectious Disease/Epidemiology
  • Molecular Genetics
  • Systems Analysis and Design

Technology Areas

  • Biotechnology