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Discovery
of the growth-link to bradyzoite differentiation—Toxoplasma
development follows a pre-determined genetic program.
In 1996, we made the key discovery that T. gondii tachyzoites emergent from a sporozoite infection
spontaneously differentiate into bradyzoites.
As they emerge from the sporozoite-infected host cell, VEG
strain tachyzoites grow very fast, like the highly virulent RH
strain.
At ~20 divisions this growth suddenly slows and the
parasites then differentiate.
Whether VEG sporozoites infect an immunocompenent or
compromised mouse strain, they develop into bradyzoites in 7 days
indicating the course of development is predetermined.
Parasite mutants trapped in the fast growth phase are
incapable of differentiating unless they are forced to slow their
growth by stress intervention.
These growth mutants are highly virulent---100 % of mice
inoculated at doses of <10 mutant parasites die in ten days
whereas inoculation of a million wild type VEG tachyzoites into
outbred mice is asymptomatic (Jerome
et al., 1998, Radke and White,
1999).
The discovery that cell cycle mechanisms are closely linked
to parasite development and influence virulence spurred the
development of our program on the regulation of Toxoplasma
growth.
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