Growth inhibition of the intestinal parasite Giardia lamblia by a dietary lectin is associated with arrest of the cell cycle.
Giardia lamblia, a cause of diarrheal disease throughout the world, is a protozoan parasite that thrives in the small intestine. It is shown here that wheat germ agglutinin (WGA), a naturally occurring lectin widely consumed in normal human diets, reversibly inhibits the growth of G. lamblia trophozoites in vitro, and reduces infection by G. muris in the adult mouse model of giardiasis. The inhibitory effect was dose related, not associated with cytotoxicity and reversed by N-acetyl-D-glucosamine in accordance with the known specificity of the lectin and in agreement with the presence of GlcNAc residues on the surface membrane of G. lamblia trophozoites. Cell cycle analysis revealed that parasites grown in the presence of WGA are arrested in the G2/M phase, providing an explanation for the lectin-induced inhibition of cell proliferation. Comparison of electrophoretic profiles by lectin blot analysis revealed both glycoprotein induction and suppression in growth-arrested organisms. Our findings raise the possibility that blocking trophozoite growth with naturally occurring dietary lectins may influence the course of giardiasis. In addition, the study of cell cycle arrest by WGA may provide a model to study the regulation of cell division in lower eukaryotes.
Ortega-Barria
E
E
Division of Geographic Medicine and Infectious Diseases, New England Medical Center, Tufts University School of Medicine, Boston, Massachusetts 02111.
Ward
H D
HD
Keusch
G T
GT
Pereira
M E
ME
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D004044:Dietary Proteins / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005872:Giardia / Q000187:drug effects / Q000254:growth & development; D016829:Giardia lamblia / Q000187:drug effects / Q000254:growth & development; D005873:Giardiasis / Q000188:drug therapy*; D006023:Glycoproteins / Q000096:biosynthesis; D037102:Lectins; D051379:Mice; D015800:Protozoan Proteins / Q000096:biosynthesis; D051381:Rats; D011975:Receptors, Mitogen / Q000378:metabolism*; D014909:Wheat Germ Agglutinins / Q000627:therapeutic use*
D004044:Dietary Proteins; D006023:Glycoproteins; D037102:Lectins; D015800:Protozoan Proteins; D011975:Receptors, Mitogen; D014909:Wheat Germ Agglutinins; C027503:wheat germ agglutinin receptor