LysR-type transcriptional regulator OvrB encoded in O island 9 drives enterohemorrhagic Escherichia coli O157:H7 virulence

Enterohemorrhagic Escherichia coli (EHEC) O157:H7 (O157) is a major foodborne pathogen that causes severe illness in humans worldwide. The genome of O157 contains 177 genomic islands known as O islands (OIs), including Shiga toxin-converting phages (OI-45 and OI-93) and the locus for enterocyte effacement (LEE) pathogenicity island (OI-148). However, most genes in OIs are uncharacterized and code for unknown functions. In this study, we demonstrated, for the first time, that OI-9 encodes a novel transcriptional activator, Z0346 (named OvrB), which is required for bacterial adherence to host cells and LEE gene expression in O157. OvrB directly binds to the promoter region of LEE1 and activates the transcription of ler (encoding a master regulator of LEE genes), which in turn activates LEE1-5 genes to promote O157 adherence. Furthermore, mouse oral infection assays showed that OvrB promotes O157 colonization in the mouse intestine. Finally, OvrB is shown to be a widespread transcriptional activator of virulence genes in other enterohemorrhagic and enteropathogenic Escherichia coli serotypes. Our work significantly expands the understanding of bacterial virulence control and provides new evidence suggesting that horizontally transferred regulator genes mediate LEE gene expression.

肠出血性大肠杆菌（EHEC）O157:H7（O157）是一种主要的食源性病原体，在全球范围内导致人类严重疾病。O157的基因组包含177个被称为O岛（OIs）的基因岛，包括志贺毒素转换噬菌体（OI - 45和OI - 93）以及肠细胞脱落（LEE）致病岛（OI - 148）。然而，OIs中的大多数基因尚未被鉴定，其编码的功能未知。在本研究中，我们首次证明OI - 9编码一种新型转录激活因子Z0346（命名为OvrB），它是O157细菌黏附宿主细胞以及LEE基因表达所必需的。OvrB直接结合到LEE1的启动子区域并激活ler（编码LEE基因的主要调控因子）的转录，进而激活LEE1 - 5基因以促进O157的黏附。此外，小鼠口服感染实验表明OvrB促进O157在小鼠肠道内的定植。最后，OvrB被证明是其他肠出血性和肠致病性大肠杆菌血清型中毒力基因的一种广泛的转录激活因子。我们的工作极大地拓展了对细菌毒力控制的理解，并提供了新的证据，表明水平转移的调控基因介导LEE基因表达。