Foster J W, Hall H K
Department of Microbiology and Immunology, College of Medicine, University of South Alabama, Mobile 36688.
J Bacteriol. 1992 Jul;174(13):4317-23. doi: 10.1128/jb.174.13.4317-4323.1992.
Fur is an important regulatory protein known to function in the presence of iron as a repressor of iron-controlled genes. It was recently discovered that Fur is also essential to Salmonella typhimurium for mounting an adaptive acid tolerance response (J. W. Foster, J. Bacteriol 173:6896-6902, 1991). Because little is known about the effect of Fur on the physiology of this enteric pathogen, a systematic two-dimensional polyacrylamide gel electrophoresis (PAGE) analysis was conducted to identify proteins whose synthesis is linked to iron levels. Mutations in the fur locus were identified and used to classify which proteins are controlled by Fur. Thirty-six proteins were overtly affected by iron availability, most of which were clearly under the control of Fur. Although most of the Fur-dependent proteins were under negative control, a significant portion (15 of 34) appeared to be under a form of positive control. Nine of the positively controlled proteins required Fur and iron for expression. However, Fur lacking iron was also required for the induction of six gene products. Surprisingly, not all iron-regulated proteins were controlled by Fur and not all Fur-dependent proteins were obviously regulated by iron status. Because fur mutants fail to mount an effective acid tolerance response, we made a comparative two-dimensional PAGE analysis of 100 total acid- and iron-regulated gene products. Production of most of these proteins was regulated by only one of the two stresses, yet a clear subset of seven genes were influenced by both acid and iron and were also controlled by fur. These proteins were also members of the acid tolerance response modulon. Consistent with the fur effect on pH-regulated protein synthesis, fur mutants lacked the inducible pH homeostasis system associated with the acid tolerance response. The results provide further evidence that Fur has an extensive impact on gene expression and cellular physiology and suggest an explanation for the acid-sensitive nature of fur mutants.
铁摄取调节蛋白（Fur）是一种重要的调节蛋白，已知其在铁存在的情况下作为铁控制基因的阻遏物发挥作用。最近发现，Fur对鼠伤寒沙门氏菌产生适应性耐酸反应也至关重要（J. W. 福斯特，《细菌学杂志》173:6896 - 6902，1991）。由于对Fur对这种肠道病原体生理学的影响了解甚少，因此进行了系统的二维聚丙烯酰胺凝胶电泳（PAGE）分析，以鉴定其合成与铁水平相关的蛋白质。鉴定了fur基因座中的突变，并用于分类哪些蛋白质受Fur控制。36种蛋白质明显受到铁可用性的影响，其中大多数显然受Fur控制。虽然大多数依赖Fur的蛋白质处于负调控之下，但很大一部分（34种中的15种）似乎处于一种正调控形式。9种受正调控的蛋白质表达需要Fur和铁。然而，诱导6种基因产物也需要缺乏铁的Fur。令人惊讶的是，并非所有铁调节蛋白都受Fur控制，也并非所有依赖Fur的蛋白质都明显受铁状态调节。由于fur突变体无法产生有效的耐酸反应，我们对总共100种酸和铁调节的基因产物进行了比较二维PAGE分析。这些蛋白质中的大多数仅受两种应激之一的调节，但有一个明确的由7个基因组成的子集受到酸和铁的影响，并且也受fur控制。这些蛋白质也是耐酸反应调节子的成员。与Fur对pH调节的蛋白质合成的影响一致，fur突变体缺乏与耐酸反应相关的可诱导pH稳态系统。结果提供了进一步的证据，表明Fur对基因表达和细胞生理学有广泛影响，并为fur突变体的酸敏感性质提供了解释。
