Shotgun proteomics of Strongyloides venezuelensis infective third stage larvae: Insights into host–parasite interaction and novel targets for diagnostics

Fonseca, Priscilla Duarte Marques; Corral, Marcelo Andreetta; Cosenza-Contreras, Miguel; Meisel, Dirce Mary Correia Lima; Melo, Gessica Baptista de; Antunes, Milena M.S.; Santo, Maria C.E.; Gryschek, Ronaldo César Borges; Costa-Cruz, Júlia Maria; Castro-Borges, William; Paula, Fabiana Martins de

doi:10.1016/j.molbiopara.2019.111249

Cited by 6 publications

(17 citation statements)

References 28 publications

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“…These include proteinases (astacins—metallopeptidases, aspartic proteases, prolyl oligopeptidase), protease inhibitors, SCP/TAPS proteins, transthyretin-like proteins and acetylcholinesterases [ 11 , 33 ]. Interestingly, the same protein families were also identified in Strongyloides venezuelensis iL3 [ 15 ]. Similarly, next generation RNA sequencing was employed to evaluate the association between larval development in an S. stercoralis laboratory strain (i.e.…”

Section: Resultsmentioning

confidence: 99%

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Novel insights into the somatic proteome of Strongyloides stercoralis infective third-stage larvae

et al. 2023

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Background Strongyloidiasis is a neglected tropical disease affecting an estimated 600 million people, particularly in resource-limited settings. The infection can persist lifelong due to unusual auto-infective cycle of Strongyloides stercoralis. The lack of a diagnostic gold standard and limited knowledge of the mechanisms underpinning this chronic infection are key issues in disease management. To date, only a few proteomics studies have been conducted to elucidate the molecular mechanisms associated with Strongyloides parasitism or to highlight novel immunological markers, with the result that our knowledge of S. stercoralis proteome remains limited. This study aims at expanding the characterization of S. stercoralis infective larvae (iL3) in order to further explore the mechanisms of parasitism and to highlight possible novel targets for serodiagnosis. Methods iL3 obtained from an infected subject were analysed by high-throughput tandem mass spectrometry. To achieve a more comprehensive characterization of the iL3 proteome we analysed the experimental dataset using an automatic search strategy combined with manual annotation, which included gene ontology (GO) analysis, InterPro annotation, assessment of the homology with Homo sapiens and other pathogens of clinical importance and B-cell epitope prediction. Results Our pipeline identified 430 S. stercoralis proteins, 187 (43%) of which were uncharacterized. Oxidoreductases and peptidases were amongst the most represented protein categories, as highlighted by molecular function GO analyses, while membrane and mitochondrial proteins were the most represented cellular component GO categories. A high proportion of proteins bearing the CAP, SCP or thioredoxin domain or belonging to cysteine-rich secretory, transthyretin-like or peptidase protein families were also identified. Additionally, we highlighted nine proteins displaying low homology with H. sapiens or other related pathogens and bearing amino acid sequences with immunogenic properties. Conclusions Our comprehensive description and annotation of the S. stercoralis iL3 proteome contribute to expanding the ‘omics characterization of this parasite and provide experimental evidence on the most represented proteins associated with S. stercoralis parasitism, as inferred from genomic and transcriptomic data. Moreover, novel candidate immunogenic proteins to be evaluated as novel serological diagnostic markers are highlighted. Graphical Abstract

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Section: Resultsmentioning

confidence: 99%

“…To date, only a few proteomics studies have been conducted to elucidate the molecular mechanisms associated with Strongyloides parasitism or to highlight novel immunological markers [11][12][13][14][15][16][17]. Consequently, our knowledge of S. stercoralis proteome is still limited.…”

Section: Introductionmentioning

confidence: 99%

Novel insights into the somatic proteome of Strongyloides stercoralis infective third-stage larvae

et al. 2023

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“…Seven protein families have been identified by other studies as expanded in the genomes of parasitic nematodes, and upregulated in parasitic life stages [35]. Studies of the Ancylostoma hookworm E/S proteome and S. venezuelensis somatic larval proteome detected some of the same families (SCP/TAPS, proteases and TTL) indicating likely presence in stool [69, 70]. To identify coproantigen diagnostic targets, we have performed a detailed analysis of 5 of the 7 parasitism-associated protein families.…”

Section: Discussionmentioning

confidence: 99%

“…(2014) [96], and analysis of S. venezuelensis somatic proteins was made by Fonseca et al . (2019) [69] which may inform further antigen searches. Vaccine candidates for S. stercoralis: sodium potassium ATPase (SsEAT), tropomyosin, and a galectin (LEC-5) [97, 98] may also generate effective antibodies for antigen capture, if the relevant antigens are detectable in stool.…”

Section: Discussionmentioning

confidence: 99%

“…As an antigen, collagen would have to be carefully analysed for species specificity and the influence of glycosylation on its availability to capture antibodies [95]. A summary of E/S proteomic studies was presented by Ditgen et al (2014) [96], and analysis of S. venezuelensis somatic proteins was made by Fonseca et al (2019) [69] which may inform further antigen searches. Vaccine candidates for S. stercoralis: sodium potassium ATPase (SsEAT), tropomyosin, and a galectin (LEC-5) [97,98] may also generate effective antibodies for antigen capture, if the relevant antigens are detectable in stool.…”

Section: Limitations and Future Workmentioning

confidence: 99%

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A comparative ‘omics’ approach for prediction of candidate Strongyloides stercoralis diagnostic coproantigens

Marlais

Bickford-Smith

Talavera-López

et al. 2022

Preprint

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Human infection with the intestinal nematode Strongyloides stercoralis is persistent unless effectively treated, and potentially fatal in immunosuppressed individuals. Epidemiological data are lacking due to inadequate diagnosis. A rapid antigen detection test is a priority for population surveillance, validating cure after treatment, and for screening prior to immunosuppression. We analysed open access 'omics' data sets and used online predictors to identify S. stercoralis proteins that are likely to be present in infected stool, Strongyloides specific, and antigenic. Transcriptomic data from gut and non-gut dwelling life cycle stages of S. stercoralis revealed 328 proteins that are differentially expressed. Strongyloides ratti proteomic data for excreted and secreted (E/S) proteins were matched to S. stercoralis , giving 1,057 orthologues. Five parasitism-associated protein families (SCP/TAPS, prolyl oligopeptidase, transthyretin-like, aspartic peptidase, acetylcholinesterase) were compared phylogenetically between S. stercoralis and outgroups, and proteins with least homology to the outgroups were selected. Proteins that overlapped between the transcriptomic and proteomic datasets were analysed by multiple sequence alignment, epitope prediction and 3D structure modelling to reveal S. stercoralis candidate peptide/protein coproantigens. We describe 22 candidates from seven genes, across all five protein families for further investigation as potential S. stercoralis diagnostic coproantigens, identified using open access data and freely-available protein analysis tools. This powerful approach can be applied to many parasitic infections with 'omic' data to accelerate development of specific diagnostic assays for laboratory or point-of-care field application.

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Diagnosis of human strongyloidiasis: Application in clinical practice

et al. 2021

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Shotgun proteomics of Strongyloides venezuelensis infective third stage larvae: Insights into host–parasite interaction and novel targets for diagnostics

Cited by 6 publications

References 28 publications

Novel insights into the somatic proteome of Strongyloides stercoralis infective third-stage larvae

Novel insights into the somatic proteome of Strongyloides stercoralis infective third-stage larvae

A comparative ‘omics’ approach for prediction of candidate Strongyloides stercoralis diagnostic coproantigens

Diagnosis of human strongyloidiasis: Application in clinical practice

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