一种新的Vibrio cholerae T3SS效应剂VopX可以调节宿主actin动态
Megan Ulbrich1, Christopher H Seward1, Andrei I Ivanov2
1Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, USA.
mBio
|January 29, 2025
概括
致病性Vibrio cholerae使用VopX效应蛋白来增强细菌殖民. VopX操纵宿主细胞的活性和信号通路,促进细菌的粘附和感染.
科学领域:
- 微生物学 微生物学
- 细胞生物学 细胞生物学
- 病变的发生和发病.
背景情况:
- 致病性Vibrio cholerae菌株用于殖民和疾病的多种毒性因素,包括III型分泌系统 (T3SS).
- 对于操纵宿主细胞而言,T3SS效应器至关重要,但它们在V. cholerae中的特定功能仍然不完全理解.
- VopX是一种T3SS效应因子,在非O1/非O139的V. cholerae菌株中被发现,涉及改变宿主细胞细胞骨架.
研究的目的:
- 为了阐明V. cholerae VopX效应蛋白的分子标和机制.
- 将酵母模型的发现转化为哺乳动物系统,以了解VopX在宿主-病原体相互作用中的功能.
- 研究VopX在调节宿主细胞细胞骨动态和细菌粘附中的作用.
主要方法:
- 在HeLa细胞中过度表达VopX以观察细胞骨变化.
- 霍乱菌株AM-19226的共同培养与极化Caco-2/BBE单层.
- 在体外生化测试以确定VopX的酶活性.
- 对VopX与RhoA和MAPK信号通路的相互作用进行分析.
主要成果:
- 过度表达VopX诱导了HeLa细胞显著的细胞圆化.
- 与V. cholerae AM-19226共同培养导致压力纤维增加,焦点粘附和Caco-2/BBE细胞粘附以VopX依赖的方式.
- VopX被确定为RhoA的关氨酸核酸交换因子 (GEF),激活MAPK信号级联.
结论:
- 通过RhoA/MAPK信号传递,VopX通过调节宿主细胞细胞骨架来促进增强的细胞-细胞外矩阵粘附.
- 这种机制可能会防止宿主细胞脱离,从而促进T3SS阳性V. cholerae.的持续细菌殖民.
- VopX代表了一种独特的毒性策略,涉及细胞骨重塑用于生产性感染.
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