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Quantitative Proteomics of Enriched Esophageal and Gut Tissues from the Human Blood Fluke Schistosoma mansoni

ABSTRACT: Schistosomes are blood-dwelling helminth parasites causing a debilitating disease in the tropics. Major challenges to control persist and vaccines would provide an additional tool, but finding protective antigens is not trivial. It's known that the self-cure response of Rhesus macaques targets proteins from the tegument, gut and esophagus, the last of which is the least investigated. Here we applied proteomics to characterise esophageal antigens with potential utility for vaccine development. This dataset was generated by partial reanalysis of our published MS-data (PXD014872; 10.1021/acs.jproteome.9b00531). Originally, we have shown that shotgun proteomics applied to dissected esophageal fragments identified 13 MEG proteins, eleven of which are uniquely located in the esophageal glands. Antigenic variation by alternative splicing of MEG proteins was confirmed together with a specialised machinery for protein glycosylation in the esophagus. Moreover some gastrodermal secretions were highly enriched in the gut, while others were more uniformly distributed, potentially as markers of lysosomal activity. In contrast to PXD014872, this reanalysis allowed semi-specific trypsin cleavage during database search. This has proven to increase N-terminal sequence coverage of proteins processed for signal peptide removal, including esophageal MEG proteins.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Leandro Neves

LAB HEAD: William de Castro Borges

PROVIDER: PXD037384 | Pride | 2024-06-20

REPOSITORIES: Pride

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			Action	DRS
	DBsearch_protein-peptides.csv	Csv
	DBsearch_proteins.csv	Csv
	LN_20160315_BE1-1.mgf	Mgf
	LN_20160315_BE1-1.raw	Raw
	LN_20160315_BE1-3.mgf	Mgf

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Quantitative Proteomics of Enriched Esophageal and Gut Tissues from the Human Blood Fluke Schistosoma mansoni

Project description:Schistosomes are blood-dwelling helminth parasites causing a debilitating disease in the tropics. Major challenges to control persist and vaccines would provide an additional tool, but their development has been problematic. During the self-cure response of Rhesus macaques, antibodies target proteins from the tegument, gut and esophagus, the last of which is the least investigated. We developed a dissection technique that permitted comparative proteomics on the schistosome esophagus and gut. A shotgun analysis applied to male heads identified 13 MEG proteins, eleven of which were uniquely located in the esophageal glands. Antigenic variation by alternative splicing of MEG proteoforms was confirmed together with a specialised machinery for protein glycosylation in the esophagus. Moreover some gastrodermal secretions were highly enriched in the gut, while others were more uniformly distributed, potentially as markers of lysosomal activity. Collectively, our findings provide a more rational, better-oriented selection of schistosome vaccine candidates in the context of a proven model of protective immunity.

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