Excretory/Secretory Proteome of Females and Males of the Hookworm

Authors

Samuel C. Uzoechi, Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Bruce A. Rosa, Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Kumar Sachin Singh, Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Young-Jun Choi, Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Bethany K. Bracken, Charles River Analytics, Inc., Cambridge, MA 02138, USA.
Paul J. Brindley, Department of Microbiology, Immunology & Tropical Medicine, Research Center for Neglected Diseases of Poverty, School of Medicine and Health Sciences, George Washington University, Washington, DC 20037, USA.
R Reid Townsend, Division of Endocrinology, Metabolism and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Robert Sprung, Division of Endocrinology, Metabolism and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Bin Zhan, Department of Pediatric Tropical Medicine, National School of Tropical Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Maria-Elena Bottazzi, Department of Pediatric Tropical Medicine, National School of Tropical Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
John M. Hawdon, Department of Microbiology, Immunology & Tropical Medicine, Research Center for Neglected Diseases of Poverty, School of Medicine and Health Sciences, George Washington University, Washington, DC 20037, USA.
Yide Wong, Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns 4878, Australia.
Alex Loukas, Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns 4878, Australia.
Sergej Djuranovic, Department of Cell Biology and Physiology, Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Makedonka Mitreva, Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.

Document Type

Journal Article

Publication Date

1-6-2023

Journal

Pathogens (Basel, Switzerland)

Volume

12

Issue

1

DOI

10.3390/pathogens12010095

Keywords

Ancylostoma ceylanicum; ESP; excretory/secretory; hookworm; proteomics

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 , 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 identified species-specific and conserved ESPs. This is the first study identifying ESPs from female and male . 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.

APA Citation

Uzoechi, Samuel C.; Rosa, Bruce A.; Singh, Kumar Sachin; Choi, Young-Jun; Bracken, Bethany K.; Brindley, Paul J.; Townsend, R Reid; Sprung, Robert; Zhan, Bin; Bottazzi, Maria-Elena; Hawdon, John M.; Wong, Yide; Loukas, Alex; Djuranovic, Sergej; and Mitreva, Makedonka, "Excretory/Secretory Proteome of Females and Males of the Hookworm" (2023). GW Authored Works. Paper 2295.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/2295

Department

Microbiology, Immunology, and Tropical Medicine