Schistosome invasion of human skin and degradation of dermal elastin are mediated by a single serine protease.
Aquatic larvae (cercariae) of the trematode parasite Schistosoma mansoni rapidly penetrate human skin by degrading host proteins including elastin. Two serine proteases, one chymotrypsin-like and the second trypsin-like, have been proposed to be involved. To evaluate the relative roles of these two proteases in larval invasion, both were purified, identified by sequence, and then biochemically characterized. The trypsin-like activity was resolved into two distinct serine proteases 76% similar in predicted amino acid sequence. Southern blot analysis, genomic polymerase chain reaction, and immunolocalization demonstrated that the trypsin-like proteases are in fact not from the schistosome, but are released with larvae from the snail host Biomphalaria glabrata. Invasion inhibition assays using selective inhibitors confirmed that the chymotrypsin-like protease is the enzyme involved in skin penetration. Its ability to degrade skin elastin was confirmed, and the three sites of cleavage within elastin help define a new family of elastases.
Salter
J P
JP
Department of Pathology and the Biomedical Sciences Graduate Program, University of California, San Francisco, California 94121, USA.
Lim
K C
KC
Hansell
E
E
Hsieh
I
I
McKerrow
J H
JH
D000595:Amino Acid Sequence; D000818:Animals; D001700:Biomphalaria / Q000201:enzymology; D002846:Chromatography, Affinity; D002850:Chromatography, Gel; D002918:Chymotrypsin / Q000378:metabolism; D003001:Cloning, Molecular; D004549:Elastin / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D007814:Larva; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D012550:Schistosoma mansoni / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012697:Serine Endopeptidases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D012867:Skin / Q000378:metabolism* / Q000469:parasitology*
D011994:Recombinant Proteins; D004549:Elastin; D012697:Serine Endopeptidases; D002918:Chymotrypsin