Haghjoo Erik, Galán Jorge E
Section of Microbial Pathogenesis, Yale University School of Medicine, Boyer Center for Molecular Medicine, New Haven, CT 06536, USA.
Mol Microbiol. 2007 Jun;64(6):1549-61. doi: 10.1111/j.1365-2958.2007.05754.x.
Salmonella enterica serovar Typhi (S. Typhi), the aetiological agent of typhoid fever, is an exclusively human pathogen. Little is known about specific factors that may confer to this bacterium its unique pathogenic features. One of these determinants is CdtB, a homologue of the active subunit of the cytolethal distending toxin, which causes DNA damage leading to cell cycle arrest and distension of intoxicated cells. A unique property of S. Typhi CdtB is that it is only synthesized when this bacterium is within an intracellular compartment. Through a genetic screen, we have identified a transcriptional regulatory protein that controls the intracellular expression of cdtB. This regulator, which we have named IgeR, is a member of the DeoR family of transcriptional regulatory proteins and is highly conserved in all S. enterica serovars. IgeR directly binds the cdtB promoter and represses its expression in the extracellular environment. Microarray analysis identified additional IgeR-regulated genes that are involved in virulence. Constitutive expression of igeR resulted in the reduction of intracellular expression of cdtB by S. Typhi and in significant impairment of the virulence of Salmonella enterica serovar Typhimurium (S. Typhimurium) in mice. We propose that IgeR may co-ordinate gene expression during Salmonella's transition from an extracellular to an intracellular environment.
伤寒沙门氏菌血清型伤寒杆菌（伤寒杆菌）是伤寒热的病原体，是一种仅感染人类的病原菌。对于可能赋予这种细菌独特致病特征的特定因素，人们了解甚少。其中一个决定因素是CdtB，它是细胞致死性膨胀毒素活性亚基的同源物，可导致DNA损伤，从而导致细胞周期停滞和中毒细胞膨胀。伤寒杆菌CdtB的一个独特特性是，只有当这种细菌处于细胞内区室时才会合成。通过基因筛选，我们鉴定出一种控制cdtB细胞内表达的转录调节蛋白。我们将这种调节蛋白命名为IgeR，它是转录调节蛋白DeoR家族的成员，在所有肠道沙门氏菌血清型中高度保守。IgeR直接结合cdtB启动子并在细胞外环境中抑制其表达。微阵列分析确定了其他与毒力相关的IgeR调节基因。igeR的组成型表达导致伤寒杆菌cdtB的细胞内表达减少，并显著损害鼠伤寒沙门氏菌（鼠伤寒杆菌）在小鼠中的毒力。我们提出，IgeR可能在沙门氏菌从细胞外环境转变为细胞内环境的过程中协调基因表达。
