Departamento de Microbiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, México.
J Bacteriol. 2012 Sep;194(18):5020-33. doi: 10.1128/JB.00915-12. Epub 2012 Jul 13.
Enteropathogenic (EPEC) and enterohemorrhagic (EHEC) Escherichia coli are clinically important diarrheagenic pathogens that adhere to the intestinal epithelial surface. The E. coli common pili (ECP), or meningitis-associated and temperature-regulated (MAT) fimbriae, are ubiquitous among both commensal and pathogenic E. coli strains and play a role as colonization factors by promoting the interaction between bacteria and host epithelial cells and favoring interbacterial interactions in biofilm communities. The first gene of the ecp operon encodes EcpR (also known as MatA), a proposed regulatory protein containing a LuxR-like C-terminal helix-turn-helix (HTH) DNA-binding motif. In this work, we analyzed the transcriptional regulation of the ecp genes and the role of EcpR as a transcriptional regulator. EHEC and EPEC ecpR mutants produce less ECP, while plasmids expressing EcpR increase considerably the expression of EcpA and production of ECP. The ecp genes are transcribed as an operon from a promoter located 121 bp upstream of the start codon of ecpR. EcpR positively regulates this promoter by binding to two TTCCT boxes distantly located upstream of the ecp promoter, thus enhancing expression of downstream ecp genes, leading to ECP production. EcpR mutants in the putative HTH DNA-binding domain are no longer able to activate ecp expression or bind to the TTCCT boxes. EcpR-mediated activation is aided by integration host factor (IHF), which is essential for counteracting the repression exerted by histone-like nucleoid-structuring protein (H-NS) on the ecp promoter. This work demonstrates evidence about the interplay between a novel member of a diverse family of regulatory proteins and global regulators in the regulation of a fimbrial operon.
肠致病性(EPEC)和肠出血性(EHEC)大肠杆菌是临床上重要的腹泻致病菌,它们附着在肠上皮表面。大肠杆菌普通菌毛(ECP)或脑膜炎相关和温度调节(MAT)纤毛在共生和致病性大肠杆菌菌株中普遍存在,通过促进细菌与宿主上皮细胞的相互作用并促进生物膜群落中细菌之间的相互作用,作为定植因子发挥作用。ecp 操纵子的第一个基因编码 EcpR(也称为 MatA),这是一种假定的调节蛋白,含有 LuxR 样 C 端螺旋-转角-螺旋(HTH)DNA 结合基序。在这项工作中,我们分析了 ecp 基因的转录调控以及 EcpR 作为转录调节剂的作用。EHEC 和 EPEC ecpR 突变体产生的 ECP 较少,而表达 EcpR 的质粒则大大增加了 EcpA 的表达和 ECP 的产生。ecp 基因作为一个操纵子从位于 ecpR 起始密码子上游 121bp 的启动子转录。EcpR 通过结合位于 ecp 启动子上游较远的两个 TTCCT 盒正向调节该启动子,从而增强下游 ecp 基因的表达,导致 ECP 产生。位于假定 HTH DNA 结合域的 ecpR 突变体不再能够激活 ecp 表达或与 TTCCT 盒结合。EcpR 介导的激活需要整合宿主因子(IHF)的辅助,IHF 对于抵消组蛋白样核结构蛋白(H-NS)对 ecp 启动子的抑制作用至关重要。这项工作证明了一种新型的多样化调节蛋白家族成员与全局调控因子在调节一个菌毛操纵子方面相互作用的证据。