Targeted disruption of the glycosylphosphatidylinositol-anchored surface antigen SAG3 gene in Toxoplasma gondii decreases host cell adhesion and drastically reduces virulence in mice.
The protozoan parasite Toxoplasma gondii is able to invade a broad range of cells within its mammalian hosts through mechanisms that are not yet fully understood. Several glycosylphosphatidylinositol-anchored antigens found in the parasite membrane are considered as major determinants in the critical interactions with the host cell. We have discovered that two of these surface antigens, SAG1 and SAG3, share significant identity, with considerable similarities in structure, suggesting an overall conserved topology. To investigate their physiological roles further, we have generated T. gondii mutants deficient in SAG3 through gene disruption. The disrupted strains display at least a twofold reduction in host cell invasion when compared with wild-type parasites. This correlated with a similar decrease in host cell adhesion in the SAG3 null mutants. Importantly, the null SAG3 mutants show attenuated infectivity, with a markedly reduced capacity to cause mortality in mice, whereas both wild-type and complemented mutants that re-expressed SAG3 were lethal at the same doses. Taken together, our results indicate that SAG3 is one member of the redundant system of T. gondii receptors that act as ligands mediating host cell recognition and attachment.
Laboratoire de Chimie Biologique, CNRS UMR 8576, Université des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq, France.
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F
Dzierszinski
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Mortuaire
M F
MF
Cesbron-Delauw
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Tomavo
D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics; D000954:Antigens, Surface / Q000235:genetics; D002448:Cell Adhesion; D005786:Gene Expression Regulation; D018390:Gene Targeting; D017261:Glycosylphosphatidylinositols / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D015800:Protozoan Proteins; D014122:Toxoplasma / Q000235:genetics* / Q000472:pathogenicity; D014124:Toxoplasmosis, Animal / Q000235:genetics* / Q000473:pathology; D014774:Virulence / Q000235:genetics
D000953:Antigens, Protozoan; D000954:Antigens, Surface; D017261:Glycosylphosphatidylinositols; D008562:Membrane Glycoproteins; D015800:Protozoan Proteins; C087692:SAG3 protein, Toxoplasma gondii