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

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 performanc...

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Main Authors: 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
Format: Article
Language:English
Published: MDPI AG 2023-01-01
Series:Pathogens
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Online Access:https://www.mdpi.com/2076-0817/12/1/95
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author 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
author_facet 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
author_sort Samuel C. Uzoechi
collection DOAJ
description 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 <i>Ancylostoma ceylanicum</i>, 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 <i>Necator americanus</i> identified species-specific and conserved ESPs. This is the first study identifying ESPs from female and male <i>A. ceylanicum</i>. 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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spelling doaj.art-872958c697284fcca62caad1f1054a2b2023-11-30T23:53:39ZengMDPI AGPathogens2076-08172023-01-011219510.3390/pathogens12010095Excretory/Secretory Proteome of Females and Males of the Hookworm <i>Ancylostoma ceylanicum</i>Samuel C. Uzoechi0Bruce A. Rosa1Kumar Sachin Singh2Young-Jun Choi3Bethany K. Bracken4Paul J. Brindley5R. Reid Townsend6Robert Sprung7Bin Zhan8Maria-Elena Bottazzi9John M. Hawdon10Yide Wong11Alex Loukas12Sergej Djuranovic13Makedonka Mitreva14Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USADivision of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USADivision of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USADivision of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USACharles River Analytics, Inc., Cambridge, MA 02138, USADepartment of Microbiology, Immunology & Tropical Medicine, Research Center for Neglected Diseases of Poverty, School of Medicine and Health Sciences, George Washington University, Washington, DC 20037, USADivision of Endocrinology, Metabolism and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USADivision of Endocrinology, Metabolism and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USADepartment of Pediatric Tropical Medicine, National School of Tropical Medicine, Baylor College of Medicine, Houston, TX 77030, USADepartment of Pediatric Tropical Medicine, National School of Tropical Medicine, Baylor College of Medicine, Houston, TX 77030, USADepartment of Microbiology, Immunology & Tropical Medicine, Research Center for Neglected Diseases of Poverty, School of Medicine and Health Sciences, George Washington University, Washington, DC 20037, USACentre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns 4878, AustraliaCentre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns 4878, AustraliaDepartment of Cell Biology and Physiology, Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USADivision of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USAThe 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 <i>Ancylostoma ceylanicum</i>, 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 <i>Necator americanus</i> identified species-specific and conserved ESPs. This is the first study identifying ESPs from female and male <i>A. ceylanicum</i>. 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.https://www.mdpi.com/2076-0817/12/1/95hookworm<i>Ancylostoma ceylanicum</i>excretory/secretoryESPproteomics
spellingShingle 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
Excretory/Secretory Proteome of Females and Males of the Hookworm <i>Ancylostoma ceylanicum</i>
Pathogens
hookworm
<i>Ancylostoma ceylanicum</i>
excretory/secretory
ESP
proteomics
title Excretory/Secretory Proteome of Females and Males of the Hookworm <i>Ancylostoma ceylanicum</i>
title_full Excretory/Secretory Proteome of Females and Males of the Hookworm <i>Ancylostoma ceylanicum</i>
title_fullStr Excretory/Secretory Proteome of Females and Males of the Hookworm <i>Ancylostoma ceylanicum</i>
title_full_unstemmed Excretory/Secretory Proteome of Females and Males of the Hookworm <i>Ancylostoma ceylanicum</i>
title_short Excretory/Secretory Proteome of Females and Males of the Hookworm <i>Ancylostoma ceylanicum</i>
title_sort excretory secretory proteome of females and males of the hookworm i ancylostoma ceylanicum i
topic hookworm
<i>Ancylostoma ceylanicum</i>
excretory/secretory
ESP
proteomics
url https://www.mdpi.com/2076-0817/12/1/95
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