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Infection and Immunity, September 2000, p. 5167-5175, Vol. 68, No. 9
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Mediation of Cryptosporidium parvum Infection In Vitro by Mucin-Like Glycoproteins Defined by a Neutralizing Monoclonal Antibody

Ana María Cevallos,1 Najma Bhat,1 Renaud Verdon,1,dagger Davidson H. Hamer,1 Barry Stein,2 Saul Tzipori,1,2 Miercio E. A. Pereira,1 Gerald T. Keusch,1 and Honorine D. Ward1,2,*

Division of Geographic Medicine and Infectious Diseases, Tupper Research Institute, New England Medical Center, Tufts University School of Medicine, Boston, Massachusetts 02111,1 and Division of Infectious Diseases, Tufts University School of Veterinary Medicine, North Grafton, Massachusetts 015362

Received 22 March 2000/Returned for modification 18 May 2000/Accepted 7 June 2000

The protozoan parasite Cryptosporidium parvum is a significant cause of diarrheal disease worldwide. Attachment to and invasion of host intestinal epithelial cells by C. parvum sporozoites are crucial steps in the pathogenesis of cryptosporidiosis. The molecular basis of these initial interactions is unknown. In order to identify putative C. parvum adhesion- and invasion-specific proteins, we raised monoclonal antibodies (MAbs) to sporozoites and evaluated them for inhibition of attachment and invasion in vitro. Using this approach, we identified two glycoproteins recognized by 4E9, a MAb which neutralized C. parvum infection and inhibited sporozoite attachment to intestinal epithelial cells in vitro. 4E9 recognized a 40-kDa glycoprotein named gp40 and a second, >220-kDa protein which was identified as GP900, a previously described mucin-like glycoprotein. Glycoproteins recognized by 4E9 are localized to the surface and apical region of invasive stages and are shed in trails from the parasite during gliding motility. The epitope recognized by 4E9 contains alpha -N-acetylgalactosamine residues, which are present in a mucin-type O-glycosidic linkage. Lectins specific for these glycans bind to the surface and apical region of sporozoites and block attachment to host cells. The surface and apical localization of these glycoproteins and the neutralizing effect of the MAb and alpha -N-acetylgalactosamine-specific lectins strongly implicate these proteins and their glycotopes as playing a role in C. parvum-host cell interactions.

* Corresponding author. Mailing address: Division of Geographic Medicine and Infectious Diseases, New England Medical Center, Box 041, 750 Washington St., Boston, MA 02111. Phone: (617) 636-7032. Fax: (617) 636-5292. E-mail: hward{at}lifespan.org.

dagger Present address: Reanimation Medicale, Maladies Infectieses et Tropicales, Centre Hospitalier Universitaire Cote-de-Nacre, Caen 14033, France.

Infection and Immunity, September 2000, p. 5167-5175, Vol. 68, No. 9
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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