Wang Qian, Wei Yi, Huang Yu, Qin Jingliang, Liu Bin, Liu Ruiying, Chen Xintong, Li Dan, Wang Qiushi, Li Xiaoya, Yang Xinyuan, Li Yuanke, Sun Hao
The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin 300457, China.
Tianjin Key Laboratory of Microbial Functional Genomics, TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin 300457, China.
Microorganisms. 2024 Jan 10;12(1):140. doi: 10.3390/microorganisms12010140.
Enterohemorrhagic (EHEC) is an important foodborne pathogen that infects humans by colonizing the large intestine. The genome of EHEC O157:H7 contains 177 unique O islands (OIs). Certain OIs significantly contribute to the heightened virulence and pathogenicity exhibited by EHEC O157:H7. However, the function of most OI genes remains unknown. We demonstrated here that EHEC O157:H7 adherence to and colonization of the mouse large intestine are both dependent on OI-97. , which is annotated as a LysR-type transcriptional regulator and encoded in OI-97, contributes to this phenotype. Z3495 activated the locus of enterocyte effacement (LEE) gene expression, promoting bacterial adherence. Deletion of significantly decreased the transcription of and other LEE genes, the ability to adhere to the host cells, and colonization in the mouse large intestine. Furthermore, the ChIP-seq results confirmed that Z3495 can directly bind to the promoter region of , which is a well-known activator of Ler, and increase LEE gene expression. Finally, phylogenetic analysis revealed that Z3495 is a widespread transcriptional regulator in enterohemorrhagic and enteropathogenic . As a result of this study, we have gained a deeper understanding of how bacteria control their virulence and provide another example of a laterally acquired regulator that regulates LEE gene expression in bacteria.
肠出血性大肠杆菌（EHEC）是一种重要的食源性病原体，通过在大肠定植感染人类。EHEC O157:H7的基因组包含177个独特的O岛（OIs）。某些O岛对EHEC O157:H7表现出的增强毒力和致病性有显著贡献。然而，大多数OI基因的功能仍然未知。我们在此证明，EHEC O157:H7对小鼠大肠的黏附和定植均依赖于OI-97。Z3495，一种注释为LysR型转录调节因子且由OI-97编码的蛋白，促成了这一表型。Z3495激活了肠细胞损伤位点（LEE）基因的表达，促进细菌黏附。Z3495的缺失显著降低了EspA和其他LEE基因的转录、黏附宿主细胞的能力以及在小鼠大肠中的定植。此外，染色质免疫沉淀测序（ChIP-seq）结果证实Z3495可直接结合到EspA的启动子区域，EspA是Ler的一个众所周知的激活因子，并增加LEE基因的表达。最后，系统发育分析表明Z3495是肠出血性和肠致病性大肠杆菌中广泛存在的转录调节因子。作为这项研究的结果，我们对细菌如何控制其毒力有了更深入的理解，并提供了另一个横向获得的调节细菌LEE基因表达的调节因子的例子。
