Proteomic characterization and comparison of the infective and adult life stage secretomes from Necator americanus and Ancylostoma ceylanicum

Yide Wong, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Australia.
Bruce A. Rosa, Department of Medicine, Washington University School of Medicine in St. Louis, St. Louis, Missouri, United States of America.
Luke Becker, Malaghan Institute of Medical Research, Wellington, New Zealand.
Mali Camberis, Malaghan Institute of Medical Research, Wellington, New Zealand.
Graham LeGros, Malaghan Institute of Medical Research, Wellington, New Zealand.
Bin Zhan, National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas, United States of America.
Maria Elena Bottazzi, National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas, United States of America.
Ricardo T. Fujiwara, Department of Parasitology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Edita Ritmejeryte, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Australia.
Thewarach Laha, Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
Sujittra Chaiyadet, Department of Tropical Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
Piyanan Taweethavonsawat, Department of Pathology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, Thailand.
Paul J. Brindley, Department of Microbiology, Immunology & Tropical Medicine, The George Washington University School of Medicine and Health Sciences, Washington, D.C., United States of America.
Bethany K. Bracken, Charles River Analytics, Cambridge, Massachusetts, United States of America.
Paul R. Giacomin, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Australia.
Makedonka Mitreva, Department of Medicine, Washington University School of Medicine in St. Louis, St. Louis, Missouri, United States of America.
Alex Loukas, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Australia.

Document Type

Journal Article

Publication Date

1-1-2025

Journal

PLoS neglected tropical diseases

Volume

19

Issue

1

DOI

10.1371/journal.pntd.0012780

Abstract

More than 470 million people globally are infected with the hookworms Ancylostoma ceylanicum and Necator americanus, resulting in an annual loss of 2.1 to 4 million disability-adjusted-life-years. Current infection management approaches are limited by modest drug efficacy, the costs associated with frequent mass drug administration campaigns, and the risk of reinfection and burgeoning drug resistance. Subunit vaccines based on proteins excreted and secreted (ES) by hookworms that reduce worm numbers and associated disease burden are a promising management strategy to overcome these limitations. However, studies on the ES proteomes of hookworms have mainly described proteins from the adult life stage which may preclude the opportunity to target the infective larva. Here, we employed high resolution mass spectrometry to identify 103 and 57 ES proteins from the infective third larvae stage (L3) as well as 106 and 512 ES proteins from the adult N. americanus and A. ceylanicum respectively. Comparisons between these developmental stages identified 91 and 41 proteins uniquely expressed in the L3 ES products of N. americanus and A. ceylanicum, respectively. We characterized these proteins based on functional annotation, KEGG pathway analysis, InterProScan signature and gene ontology. We also performed reciprocal BLAST analysis to identify orthologs across species for both the L3 and adult stages and identified five orthologous proteins in both life stages and 15 proteins that could be detected only in the L3 stage of both species. Last, we performed a three-way reciprocal BLAST on the L3 proteomes from both hookworm species together with a previously reported L3 proteome from the rodent hookworm Nippostrongylus brasiliensis, and identified eight L3 proteins that could be readily deployed for testing using well established rodent models. This novel characterization of L3 proteins and taxonomic conservation across hookworm species provides a raft of potential candidates for vaccine discovery for prevention of hookworm infection and disease.

Department

Microbiology, Immunology, and Tropical Medicine

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