Toxopain-1 is critical for infection in a novel chicken embryo model of congenital toxoplasmosis.
We tested the hypothesis that cathepsins and specifically toxopain-1, a cathepsin B, play a critical role in the pathogenesis of toxoplasmosis. We found that inhibiting the expression of toxopain-1-specific mRNA and protein by >60% significantly decreased the capacity of the parasites to multiply and invade in vitro. To relate these in vitro results to the role of toxopain-1 in pathogenesis in vivo, we developed a novel chicken embryo model of congenital toxoplasmosis. Inhibiting either toxopain-1 expression or specific cysteine proteinase activity significantly reduced congenital infection of chicken embryos, as determined by histopathology and by the number of parasites quantified by real-time PCR. Our new model provides key in vivo validation for the hypothesis that toxopain-1 is a potential drug target in Toxoplasma gondii and also provides a new animal model for rapid, inexpensive screening of antiparasitic compounds.
Que
Xuchu
X
Departments of Pathology and Medicine, University of California, San Diego, California 92103-8416, USA.
Wunderlich
Annette
A
Joiner
Keith A
KA
Reed
Sharon L
SL
D000818:Animals; D001483:Base Sequence; D002642:Chick Embryo; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000502:physiology*; D016054:DNA, Protozoan / Q000235:genetics; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects; D017125:Genes, Protozoan; D006801:Humans; D066298:In Vitro Techniques; D016372:RNA, Antisense / Q000235:genetics / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016053:RNA, Protozoan / Q000235:genetics / Q000378:metabolism; D013045:Species Specificity; D014122:Toxoplasma / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D014124:Toxoplasmosis, Animal / Q000209:etiology* / Q000473:pathology; D016781:Toxoplasmosis, Cerebral / Q000209:etiology / Q000473:pathology; D014125:Toxoplasmosis, Congenital / Q000209:etiology* / Q000473:pathology
D016054:DNA, Protozoan; D016372:RNA, Antisense; D012333:RNA, Messenger; D016053:RNA, Protozoan; D003546:Cysteine Endopeptidases; C462508:toxopain-1, Toxoplasma gondii