A Secreted Serine-Threonine Kinase Determines Virulence in the Eukaryotic Pathogen <i>Toxoplasma gondii</i>

TLDR

Toxoplasma gondii strains differ dramatically in virulence despite being genetically very similar. Positional cloning identified the candidate virulence gene ROP18, a highly polymorphic serine‑threonine kinase secreted into the host cell during parasite invasion. Genetic mapping revealed two closely adjacent quantitative trait loci on chromosome VIIa controlling extreme virulence of the type I lineage, and transfection of the virulent ROP18 allele into a nonpathogenic type III strain increased growth and mortality by 4–5 logs, demonstrating that ROP18’s kinase activity and secretion of effectors are major components of parasite virulence.

Abstract

Toxoplasma gondii strains differ dramatically in virulence despite being genetically very similar. Genetic mapping revealed two closely adjacent quantitative trait loci on parasite chromosome VIIa that control the extreme virulence of the type I lineage. Positional cloning identified the candidate virulence gene ROP18 , a highly polymorphic serine-threonine kinase that was secreted into the host cell during parasite invasion. Transfection of the virulent ROP18 allele into a nonpathogenic type III strain increased growth and enhanced mortality by 4 to 5 logs. These attributes of ROP18 required kinase activity, which revealed that secretion of effectors is a major component of parasite virulence.