Revisiting the<i>Ancylostoma caninum</i>secretome provides new information on hookworm-host interactions

Morante, Taylor; Shepherd, Catherine; Constantinoiu, Constantin; Loukas, Alex; Sotillo, Javier

doi:10.1101/139006

Cited by 6 publications

(5 citation statements)

References 31 publications

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“…We identified secretomes from species in all five major clades in the phylum Nematoda, with several independent transitions from free-living to vertebrate parasitism [ 34 , 35 ]. We included secretomes of Haemonchus contortus [ 36 , 37 ], Ancylostoma caninum [ 38 , 39 ], Heligmosomoides polygyrus bakeri [ 24 , 40 ], Nippostrongylus brasiliensis [ 41 ], Necator americanus [ 42 ], Strongyloides ratti [ 43 ], Strongyloides venezuelensis [ 44 ], Ascaris suum [ 45 – 47 ], Dirofilaria immitis [ 48 , 49 ], Brugia malayi [ 50 – 52 ], Onchocerca ochengi [ 53 ], Litomosoides sigmodontis [ 54 ], Spirocerca lupi [ 55 ], Gnathostoma spinigerum [ 56 ], Trichuris muris [ 57 ], and Trichuris suis [ 58 ]. Plant parasitic species included Meloidogyne incognita [ 16 ], Bursaphelenchus xylophilus [ 59 , 60 ], and Bursaphelenchus mucronatus [ 59 ].…”

Section: Methodsmentioning

confidence: 99%

Mining nematode protein secretomes to explain lifestyle and host specificity

et al. 2021

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Parasitic nematodes are highly successful pathogens, inflicting disease on humans, animals and plants. Despite great differences in their life cycles, host preference and transmission modes, these parasites share a common capacity to manipulate their host’s immune system. This is at least partly achieved through the release of excretory/secretory proteins, the most well-characterized component of nematode secretomes, that are comprised of functionally diverse molecules. In this work, we analyzed published protein secretomes of parasitic nematodes to identify common patterns as well as species-specific traits. The 20 selected organisms span 4 nematode clades, including plant pathogens, animal parasites, and the free-living species Caenorhabditis elegans. Transthyretin-like proteins were the only component common to all adult secretomes; many other protein classes overlapped across multiple datasets. The glycolytic enzymes aldolase and enolase were present in all parasitic species, but missing from C. elegans. Secretomes from larval stages showed less overlap between species. Although comparison of secretome composition across species and life-cycle stages is challenged by the use of different methods and depths of sequencing among studies, our workflow enabled the identification of conserved protein families and pinpointed elements that may have evolved as to enable parasitism. This strategy, extended to more secretomes, may be exploited to prioritize therapeutic targets in the future.

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Section: Methodsmentioning

confidence: 99%

Mining nematode protein secretomes to explain lifestyle and host specificity

et al. 2021

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“…SCP/TAPS, also referred to as venom allergen-like or Activation-associated Secreted Proteins (ASPs) (Pfam accession number no. PF00188) have been reported from many helminths, but appear to be significantly expanded in the genomes and secreted proteomes of gut-resident clade IV and V parasitic nematodes, including the hookworms [11,[18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Comprehensive analysis of the secreted proteome of adult Necator americanus hookworms

et al. 2020

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The human hookworm Necator americanus infects more than 400 million people worldwide, contributing substantially to the poverty in these regions. Adult stage N. americanus live in the small intestine of the human host where they inject excretory/secretory (ES) products into the mucosa. ES products have been characterized at the proteome level for a number of animal hookworm species, but until now, the difficulty in obtaining sufficient live N. americanus has been an obstacle in characterizing the secretome of this important human pathogen. Herein we describe the ES proteome of N. americanus and utilize this information along with RNA Seq data to conduct the first proteogenomic analysis of a parasitic helminth, significantly improving the available genome and thereby generating a robust description of the parasite secretome. The genome annotation resulted in a revised prediction of 3,425 fewer genes than initially reported, accompanied by a significant increase in the number of exons and introns, total gene length and the percentage of the genome covered by genes. Almost 200 ES proteins were identified by LC-MS/MS with SCP/TAPS proteins, 'hypothetical' proteins and proteases among the most abundant families. These proteins were compared to commonly used model species of human parasitic infections, including Ancylostoma caninum, Nippostrongylus brasiliensis and Heligmosomoides polygyrus. SCP/ TAPS proteins are immunogenic in nematode infections, so we expressed four of those identified in this study in recombinant form and showed that they are all recognized to varying degrees by serum antibodies from hookworm-infected subjects from a disease-endemic area of Brazil. Our findings provide valuable information on important families of proteins a1111111111 a1111111111 a1111111111 a1111111111 a1111111111

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“…As one of the most intensive research areas, a pleiotropic range of immunomodulatory activities of ES proteins has been determined in numerous species of GIhelminths, including H. polygyrus [65], Teladorsagia circumcincta [66], A. caninum [67], and N. americanus [68]. However, the role of individual ES components is still being elaborated or has yet to be determined in most instances.…”

Section: Discussionmentioning

confidence: 99%

Proteomic analysis revealed T cell hyporesponsiveness induced by Haemonchus contortus excretory and secretory proteins

Tian

Zhang

et al. 2020

Vet Res

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Haemonchus contortus has evolved highly integrated and sophisticated mechanisms to promote coexistence with hosts. The excretory-secretory (ES) products generated by this parasite contribute to the regulation of the host immune response to facilitate immune evasion and induce chronicity, but the proteins responsible for this process and the exact cellular mechanisms have yet to be defined. In this study, we identified 114 H. contortus ES proteins (HcESPs) interacting with host T cells and 15 T cell binding receptors via co-immunoprecipitation and shotgun liquid chromatography-tandem mass spectrometry analysis. Based on bioinformatics analysis, we demonstrated that HcESPs could inhibit T cell viability, induce cell apoptosis, suppress T cell proliferation and cause cell cycle arrest. Furthermore, the stimulation of HcESPs exerted critical control effects on T cell cytokine production profiles, predominantly promoting the secretion of interleukin (IL)-10, IL-17A and transforming growth factor-β1 and inhibiting IL-2, IL-4 and interferon-γ production. Collectively, these findings may provide insights into the interaction between ES proteins and key host effector cells, enhancing our understanding of the molecular mechanism underlying parasite immune evasion and providing new clues for novel vaccine development.

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Revisiting theAncylostoma caninumsecretome provides new information on hookworm-host interactions

Cited by 6 publications

References 31 publications

Mining nematode protein secretomes to explain lifestyle and host specificity

Mining nematode protein secretomes to explain lifestyle and host specificity

Comprehensive analysis of the secreted proteome of adult Necator americanus hookworms

Proteomic analysis revealed T cell hyporesponsiveness induced by Haemonchus contortus excretory and secretory proteins

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