A NOVEL MULTIDOMAIN MUCIN-LIKE GLYCOPROTEIN OF CRYPTOSPORIDIUM-PARVUMMEDIATES INVASION

Cryptosporidium parvum is a protozoan parasite which produces self-lim ited disease in immunocompetent hosts and devastating, persistent diar rhea in immunocompromised individuals. There is no effective treatment for cryptosporidiosis and little is known about the basic biology of the organism. Cloning and sequence analysis of the gene encoding GP900 , a previously identified >900 kDa glycoprotein, predicts a mucin-like glycoprotein composed of distal cysteine-rich domains separated by po lythreonine domains and a large membrane proximal N-glycosylated core region. A trinucleotide repeat composed predominantly of the triplet A CA encodes the threonine domains. GP900 is stored in micronemes prior to appearance on the surface of invasive forms. The concentration of n ative GP900 which inhibits 50% (IC50) of invasion in vitro is low pico molar; the IC,, for a recombinant cysteine rich-domain is low nanomola r. These observations indicate that GP900 is a parasite ligand for a h ost receptor involved in attachment/invasion and suggest that immunoth erapy or chemotherapy directed against GP900 may be feasible. (C) 1998 Elsevier Science B.V. All rights reserved.