title: Differential use of protease families for invasion by schistosome cercariae.
abstract: Schistosomes are parasitic platyhelminths (flatworms) of birds and mammals. As a parasitic disease of humans, schistosomiasis ranks second only to malaria in global importance. Schistosome larvae (cercariae) must invade and penetrate skin as an initial step to successful infection of the vertebrate host. Proteolytic enzymes secreted from the acetabular glands of cercariae contribute significantly to the invasion process. In this comparative study, we analyzed protease activities secreted by cercariae of Schistosoma mansoni, Schistosoma japonicum and Schistosomatium douthitti. Using protease-family specific, irreversible active-site probes, fluorogenic peptidyl substrates, immuno-histochemistry and high-resolution mass spectrometry, considerable species differences were noted in the quantity and character of proteases. Serine proteases, the most abundant enzymes secreted by S. mansoni cercariae, were not identified in S. japonicum. In contrast, the acetabular gland contents of S. japonicum cercariae had a 40-fold greater cathepsin B-like activity than those of S. mansoni. Based on the present data and previous reports, we propose that cysteine proteases represent an archetypal tool for tissue invasion among primitive metazoa and the use of serine proteases arose later in schistosome evolution. Computational analysis of serine protease phylogeny revealed an extraordinarily distant relationship between S. mansoni serine proteases and other members of the Clan PA family S1 proteases.
authors.affiliation: Sandler Center for Basic Research in Parasitic Diseases, California Institute for Quantitative Biomedical Research (QB3), 1700 4th Street, University of California, San Francisco, CA 94158-2550, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Dvorák
authors.forename: Susan T
authors.initials: ST
authors.lastname: Mashiyama
authors.forename: Simon
authors.initials: S
authors.lastname: Braschi
authors.forename: Mohammed
authors.initials: M
authors.lastname: Sajid
authors.forename: Giselle M
authors.initials: GM
authors.lastname: Knudsen
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hansell
authors.forename: Kee-Chong
authors.initials: KC
authors.lastname: Lim
authors.forename: Ivy
authors.initials: I
authors.lastname: Hsieh
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Bahgat
authors.forename: Bryony
authors.initials: B
authors.lastname: Mackenzie
authors.forename: Katalin F
authors.initials: KF
authors.lastname: Medzihradszky
authors.forename: Patricia C
authors.initials: PC
authors.lastname: Babbitt
authors.forename: Conor R
authors.initials: CR
authors.lastname: Caffrey
authors.forename: James H
authors.initials: JH
authors.lastname: McKerrow
mesh_terms: D000818:Animals; D002401:Cathepsin B / Q000737:chemistry / Q000378:metabolism*; D002918:Chymotrypsin / Q000378:metabolism; D022761:Gene Transfer, Horizontal; D007814:Larva / Q000201:enzymology / Q000472:pathogenicity; D013058:Mass Spectrometry; D010802:Phylogeny; D040901:Proteomics; D012549:Schistosoma japonicum / Q000201:enzymology* / Q000254:growth & development / Q000472:pathogenicity; D012550:Schistosoma mansoni / Q000201:enzymology*; D012551:Schistosomatidae / Q000201:enzymology; D012697:Serine Endopeptidases / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D013045:Species Specificity
chemical_list: D012697:Serine Endopeptidases; D002918:Chymotrypsin; D002401:Cathepsin B