期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2017
卷号：114
期号：48
页码：12785-12790
DOI：10.1073/pnas.1713008114
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Bacterial cells modulate transcription in response to changes in iron availability. The ferric uptake regulator (Fur) senses intracellular iron availability and plays a central role in maintaining iron homeostasis in Bacillus subtilis . Here we utilized FrvA, a high-affinity Fe2+ efflux transporter from Listeria monocytogenes , as an inducible genetic tool to deplete intracellular iron. We then characterized the responses of the Fur, FsrA, and PerR regulons as cells transition from iron sufficiency to deficiency. Our results indicate that the Fur regulon is derepressed in three distinct waves. First, uptake systems for elemental iron ( efeUOB ), ferric citrate ( fecCDEF ), and petrobactin ( fpbNOPQ ) are induced to prevent iron deficiency. Second, B. subtilis synthesizes its own siderophore bacillibactin ( dhbACEBF ) and turns on bacillibactin ( feuABC ) and hydroxamate siderophore ( fhuBCGD ) uptake systems to scavenge iron from the environment and flavodoxins ( ykuNOP ) to replace ferredoxins. Third, as iron levels decline further, an “iron-sparing” response ( fsrA , fbpAB , and fbpC ) is induced to block the translation of abundant iron-utilizing proteins and thereby permit the most essential iron-dependent enzymes access to the limited iron pools. ChIP experiments demonstrate that in vivo occupancy of Fur correlates with derepression of each operon, and the graded response observed here results, at least in part, from higher-affinity binding of Fur to the “late”-induced genes.
