title: Excretion/secretion products from Schistosoma mansoni adults, eggs and schistosomula have unique peptidase specificity profiles.
abstract: 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.
authors.affiliation: 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.
authors.forename: Jan
authors.initials: J
authors.lastname: Dvořák
authors.affiliation: 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.
authors.forename: Pavla
authors.initials: P
authors.lastname: Fajtová
authors.affiliation: 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.
authors.forename: Lenka
authors.initials: L
authors.lastname: Ulrychová
authors.affiliation: 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.
authors.forename: Adrian
authors.initials: A
authors.lastname: Leontovyč
authors.affiliation: Center for Discovery and Innovation in Parasitic Diseases and the Department of Pathology, University of California San Francisco, San Francisco, CA 94158, USA.
authors.forename: Liliana
authors.initials: L
authors.lastname: Rojo-Arreola
authors.affiliation: Center for Discovery and Innovation in Parasitic Diseases and the Department of Pathology, University of California San Francisco, San Francisco, CA 94158, USA.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Suzuki
authors.affiliation: Institute of Organic Chemistry and Biochemistry, The Czech Academy of Sciences, Prague CZ - 166 10, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Horn
authors.affiliation: Institute of Organic Chemistry and Biochemistry, The Czech Academy of Sciences, Prague CZ - 166 10, Czech Republic.
authors.forename: Michael
authors.initials: M
authors.lastname: Mareš
authors.affiliation: Dept. of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94158, USA.
authors.forename: Charles S
authors.initials: CS
authors.lastname: Craik
authors.affiliation: Center for Discovery and Innovation in Parasitic Diseases and the Department of Pathology, University of California San Francisco, San Francisco, CA 94158, USA.
authors.forename: Conor R
authors.initials: CR
authors.lastname: Caffrey
authors.affiliation: Dept. of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94158, USA. Electronic address: ajodonoghue@ucsd.edu.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: O'Donoghue
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D015801:Helminth Proteins / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D008018:Life Cycle Stages; D008969:Molecular Sequence Data; D010063:Ovum / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism*; D059748:Proteolysis; D012550:Schistosoma mansoni / Q000254:growth & development / Q000378:metabolism* / Q000502:physiology; D012555:Schistosomiasis mansoni / Q000469:parasitology; D013379:Substrate Specificity
chemical_list: D015801:Helminth Proteins; D010447:Peptide Hydrolases
keywords: Excretion; Fluke; Inhibitor; Parasite; Protease; Secretion