铁硫集群需求的IscR介导传感协调了Yersinia伪结核病中的毒性基因表达
bioRxiv : the preprint server for biology
|November 24, 2025
概括
Yersinia pseudotuberculosis通过将III型分泌系统 (T3SS) 和YadA粘合素与铁硫 (Fe-S) 集群需求联系起来来微调毒性因子表达. 改变这种调节会在感染期间损害细菌的健康.
科学领域:
- 微生物学 微生物学
- 细菌病原体的产生
- 分子生物学分子生物学
背景情况:
- 第三类分泌系统 (T3SS) 对于像Yersinia pseudotuberculosis这样的病原体的毒性至关重要,但由于代谢成本,其表达受到严格监管.
- 铁硫 (Fe-S) 集群协调转录因子IscR感知铁和氧气水平,影响Yersinia和其他病原体的毒性基因表达.
- 之前的研究表明,无集群的apo-IscR在高FeS需求 (有氧,低铁) 下促进T3SS和YadA表达,促进感染.
研究的目的:
- 研究如何改变IscR结合特异性对lcrF促进体影响Yersinia病毒性因子表达对铁和氧的反应.
- 为了确定反向铁和氧气调节毒性因子对宿主环境中的Yersinia感染动态的影响.
主要方法:
- 设计了一种Yersinia伪结核突变种 (lcrF^pTypeI) 具有改变了对 [2Fe-2S] - IscR.I 的lcrF促进体结合特异性.
- 在不同的铁和氧条件下评估LcrF,T3SS和YadA的表达.
- 利用带有条形码的Y.伪结核菌株来分析感染动态和确定体内瓶.
主要成果:
- 在低Fe-S需求 (无氧,铁充足的条件) 下,lcrF^pTypeI突变体表现出LcrF,T3SS和YadA的过度表达.
- 这种调节的逆转表明,IscR结合的特异性决定了毒性因子对铁和氧的反应.
- 突变者在阴中经历了显著的瓶,表明在特定的宿主微环境中适应性降低.
结论:
- 将T3SS和YadA表达与细胞Fe-S集群需求联系在一起,使Yersinia能够将其毒性谱适应宿主组织微环境.
- 从宿主组织线索中解离毒性基因表达,通过逆转IscR介导的调节,降低了细菌的适应性.
- IscR在协调细菌毒性与宿主环境条件方面发挥着关键作用,影响感染的进展.
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