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 (2023) Excretory/Secretory Proteome of Females and Males of the Hookworm Ancylostoma ceylanicum. Pathogens, 12 (1). 95.

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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.

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