Scholarlink

<p><i>Toxoplasma gondii</i> parasites exhibit extraordinary host promiscuity owing to over 250 putative secreted proteins that disrupt host cell functions, enabling parasite persistence. However, most of the known effector proteins are specific to <i>Toxoplasma</i> genotypes or hosts. To identify virulence factors that function across different parasite isolates and mouse strains that differ in susceptibility to infection, we performed systematic pooled in vivo CRISPR-Cas9 screens targeting the <i>Toxoplasma</i> secretome. We identified several proteins required for infection across parasite strains and mouse species, of which the dense granule protein 12 (GRA12) emerged as the most important effector protein during acute infection. GRA12 deletion in IFNγ-activated macrophages results in collapsed parasitophorous vacuoles and increased host cell necrosis, which is partially rescued by inhibiting early parasite egress. GRA12 orthologues from related coccidian parasites, including <i>Neospora caninum</i> and <i>Hammondia hammondi</i>, complement TgΔGRA12 in vitro, suggesting a common mechanism of protection from immune clearance by their hosts.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

GRA12 is a common virulence factor across Toxoplasma gondii strains and mouse subspecies

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年4月16日

查看全文
  • Francesca Torelli,
  • Simon Butterworth,
  • Eloise Lockyer,
  • Ana N. Matias,
  • Franziska Hildebrandt,
  • Ok-Ryul Song,
  • Jennifer Pearson-Farr,
  • Moritz Treeck

摘要

Toxoplasma gondii parasites exhibit extraordinary host promiscuity owing to over 250 putative secreted proteins that disrupt host cell functions, enabling parasite persistence. However, most of the known effector proteins are specific to Toxoplasma genotypes or hosts. To identify virulence factors that function across different parasite isolates and mouse strains that differ in susceptibility to infection, we performed systematic pooled in vivo CRISPR-Cas9 screens targeting the Toxoplasma secretome. We identified several proteins required for infection across parasite strains and mouse species, of which the dense granule protein 12 (GRA12) emerged as the most important effector protein during acute infection. GRA12 deletion in IFNγ-activated macrophages results in collapsed parasitophorous vacuoles and increased host cell necrosis, which is partially rescued by inhibiting early parasite egress. GRA12 orthologues from related coccidian parasites, including Neospora caninum and Hammondia hammondi, complement TgΔGRA12 in vitro, suggesting a common mechanism of protection from immune clearance by their hosts.