A lone amino acid change determines success or failure for strains of Toxoplasma gondii, say Yamamoto et al. The group identifies a kinase mutation that thwarts one strain's ability to activate Stat3 and halt the host immune response.

T. gondii comes in three chief flavors: types I, II, and III. Unfortunately for types II and III, their genetic differences severely cripple infectivity. The genetic changes in type II parasites disable T. gondii's ability to down-regulate protective host cytokines by turning on the Stat3 transcription factor. Exactly how the type I parasite activates Stat3 was unknown, but a polymorphism was recently mapped to a gene encoding a secretory organelle kinase called ROP16. And inserting type I ROP16 into type II parasites helped them activate Stat3.

Yamamoto et al. have now created a type I strain that lacks ROP16. Like normal type II parasites, the type I mutant failed to activate Stat3 and as a result induced host cytokines. Expression of ROP16 in mammalian cells, on the other hand, pumped up STAT3 activity by triggering its phosphorylation and nuclear translocation.

ROP16 kinase activity was necessary for Stat3 activation, and in vitro evidence suggested the phosphorylation may be direct, as ROP16 directly bound to and phosphorylated Stat3. The group found that a single leucine-to-serine substitution in type II ROP16 disabled Stat3 activation. The residue is not essential for kinase activity, but in silico modeling suggested the serine creates a misshapen active site. NL