Schistosomiasis is one of a number of chronic helminth diseases of poverty that severely impact personal and societal well-being and productivity. Peptidases (proteases) are vital to successful parasitism, and can modulate host physiology and immunology. Interference of peptidase action by specific drugs or vaccines can be therapeutically beneficial. To date, research on peptidases in the schistosome parasite has focused on either the functional characterization of individual peptidases or their annotation as part of global genome or transcriptome studies. We were interested in functionally characterizing the complexity of peptidase activity operating at the host-parasite interface, therefore the excretory-secretory products of key developmental stages of Schistosoma mansoni that parasitize the human were examined. Using class specific peptidase inhibitors in combination with a multiplex substrate profiling assay, a number of unique activities derived from endo- and exo-peptidases were revealed in the excretory-secretory products of schistosomula (larval migratory worms), adults and eggs. The data highlight the complexity of the functional degradome for each developmental stage of this parasite and facilitate further enquiry to establish peptidase identity, physiological and immunological function, and utility as drug or vaccine candidates.

1st Faculty of Medicine Charles University Prague Prague CZ 121 08 Czech Republic

Center for Discovery and Innovation in Parasitic Diseases and the Department of Pathology University of California San Francisco San Francisco CA 94158 USA

Dept of Parasitology Faculty of Science Charles University Prague Prague CZ 128 44 Czech Republic

Dept of Pharmaceutical Chemistry University of California San Francisco San Francisco CA 94158 USA

Institute of Molecular Genetics The Czech Academy of Sciences Prague CZ 142 20 Czech Republic

Institute of Organic Chemistry and Biochemistry The Czech Academy of Sciences Prague CZ 166 10 Czech Republic

Institute of Parasitology Biology Center The Czech Academy of Sciences České Budějovice CZ 370 05 Czech Republic

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$a Dvořák, Jan $u Institute of Molecular Genetics, The Czech Academy of Sciences, Prague CZ - 142 20, Czech Republic; Institute of Parasitology, Biology Center, The Czech Academy of Sciences, České Budějovice CZ - 370 05, Czech Republic; Institute of Organic Chemistry and Biochemistry, The Czech Academy of Sciences, Prague CZ - 166 10, Czech Republic.

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$a Excretion/secretion products from Schistosoma mansoni adults, eggs and schistosomula have unique peptidase specificity profiles / $c J. Dvořák, P. Fajtová, L. Ulrychová, A. Leontovyč, L. Rojo-Arreola, BM. Suzuki, M. Horn, M. Mareš, CS. Craik, CR. Caffrey, AJ. O'Donoghue,

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$a Schistosomiasis is one of a number of chronic helminth diseases of poverty that severely impact personal and societal well-being and productivity. Peptidases (proteases) are vital to successful parasitism, and can modulate host physiology and immunology. Interference of peptidase action by specific drugs or vaccines can be therapeutically beneficial. To date, research on peptidases in the schistosome parasite has focused on either the functional characterization of individual peptidases or their annotation as part of global genome or transcriptome studies. We were interested in functionally characterizing the complexity of peptidase activity operating at the host-parasite interface, therefore the excretory-secretory products of key developmental stages of Schistosoma mansoni that parasitize the human were examined. Using class specific peptidase inhibitors in combination with a multiplex substrate profiling assay, a number of unique activities derived from endo- and exo-peptidases were revealed in the excretory-secretory products of schistosomula (larval migratory worms), adults and eggs. The data highlight the complexity of the functional degradome for each developmental stage of this parasite and facilitate further enquiry to establish peptidase identity, physiological and immunological function, and utility as drug or vaccine candidates.

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$a Fajtová, Pavla $u Institute of Organic Chemistry and Biochemistry, The Czech Academy of Sciences, Prague CZ - 166 10, Czech Republic; First Faculty of Medicine, Charles University in Prague, Prague CZ - 121 08, Czech Republic.

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$a Ulrychová, Lenka $u Institute of Molecular Genetics, The Czech Academy of Sciences, Prague CZ - 142 20, Czech Republic; Dept. of Parasitology, Faculty of Science, Charles University in Prague, Prague CZ - 128 44, Czech Republic.

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$a Leontovyč, Adrian $u Institute of Organic Chemistry and Biochemistry, The Czech Academy of Sciences, Prague CZ - 166 10, Czech Republic; First Faculty of Medicine, Charles University in Prague, Prague CZ - 121 08, Czech Republic.

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$a Rojo-Arreola, Liliana $u Center for Discovery and Innovation in Parasitic Diseases and the Department of Pathology, University of California San Francisco, San Francisco, CA 94158, USA.

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$a Suzuki, Brian M $u Center for Discovery and Innovation in Parasitic Diseases and the Department of Pathology, University of California San Francisco, San Francisco, CA 94158, USA.

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$a Horn, Martin $u Institute of Organic Chemistry and Biochemistry, The Czech Academy of Sciences, Prague CZ - 166 10, Czech Republic.

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$a Mareš, Michael $u Institute of Organic Chemistry and Biochemistry, The Czech Academy of Sciences, Prague CZ - 166 10, Czech Republic.

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$a Craik, Charles S $u Dept. of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94158, USA.

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$a Caffrey, Conor R $u Center for Discovery and Innovation in Parasitic Diseases and the Department of Pathology, University of California San Francisco, San Francisco, CA 94158, USA.

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$a O'Donoghue, Anthony J $u Dept. of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94158, USA. Electronic address: ajodonoghue@ucsd.edu.

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