A secreted serine-threonine kinase determines virulence in the eukaryotic pathogen Toxoplasma gondii

被引:412
作者
Taylor, S.
Barragan, A.
Su, C.
Fux, B.
Fentress, S. J.
Tang, K.
Beatty, W. L.
El Hajj, H.
Jerome, M.
Behnke, M. S.
White, M.
Wootton, J. C.
Sibley, L. D. [1 ]
机构
[1] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63130 USA
[2] Karolinska Inst, Swedish Inst Infect Dis Control, Dept Med, S-14186 Stockholm, Sweden
[3] Karolinska Inst, Ctr Infect Med, Dept Med, S-14186 Stockholm, Sweden
[4] Univ Tennessee, Dept Microbiol, Knoxville, TN 37996 USA
[5] Univ Montpellier 2, UMR 5539, CNRS, F-34095 Montpellier 5, France
[6] Montana State Univ, Dept Vet Mol Biol, Bozeman, MT 59717 USA
[7] NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA
关键词
PARASITOPHOROUS VACUOLE; INTRACELLULAR PARASITE; STRAINS; INFECTION; REVEALS; OVERPRODUCTION; RECOMBINATION; TRANSMISSION; APOPTOSIS; LINEAGES;
D O I
10.1126/science.1133643
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:1776 / 1780
页数:5
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