Bradyrhizobium japonicum senses iron through the status of haem to regulate iron homeostasis and metabolism

Abstract

SummaryThe Irr protein from the bacterium Bradyrhizobium japonicum is expressed under iron limitation to mediate iron control of haem biosynthesis. The regulatory input to Irr is the status of haem and its precursors iron and protoporphyrin at the site of haem synthesis. Here, we show that Irr controls the expression of iron transport genes and many other iron-regulated genes not directly involved in haem synthesis. Irr is both a positive and negative effector of gene expression, and in at least some cases the control is direct. Loss of normal iron responsiveness of those genes in an irr mutant, as well as a lower total cellular iron content, suggests that Irr is required for the correct perception of the cellular iron status. Degradation of Irr in iron replete cells requires haem. Accordingly, control of Irr-regulated genes by iron was aberrant in a haem-defective strain, and iron replete mutant cells behave as if they are iron-limited. In addition, the haem mutant had an abnormally high cellular iron content. The findings indicate that B. japonicum senses iron via the status of haem biosynthesis in an Irr-dependent manner to regulate iron homeostasis and metabolism.

Antiparallel and Interlinked Control of Cellular Iron Levels by the Irr and RirA Regulators of Agrobacterium tumefaciens

“…This reciprocal regulation via Irr and RirA allows A. tumefaciens to accumulate sufficient cellular iron pools and grow efficiently under iron-limited conditions. The irr-null mutant cannot mount the proper low-iron regulatory response, resulting in a decreased cellular iron pool similar to the decrease in total iron content observed in B. japonicum, as well as a dramatic growth yield defect (74). This is presumably through a combination of unregulated consumption of iron and the limited expression of iron uptake systems.…”

Control of bacterial iron homeostasis by manganese

“…To further address the effects of manganese on iron metabolism, we examined the expression of several genes known to be regulated by iron at the mRNA level in B. japonicum wild-type cells. blr3555 and bll4920 encode iron siderophore transport outer-membrane receptors, and blr6519 encodes an iron-independent fumarase, which replaces the iron-sulfur fumarase when the metal is limiting (15,17,25). Cells were grown under various iron or manganese conditions, and mRNA encoding each gene was examined by quantitative realtime PCR (qPCR).…”

“…The Irr protein is a global iron regulator in B. japonicum (14,15). Most genes that are strongly regulated by iron are directly or indirectly controlled by Irr (14,15).…”

“…Most genes that are strongly regulated by iron are directly or indirectly controlled by Irr (14,15). Irr functions under iron limitation, and binds to the promoters of target genes to positively or negatively regulate gene expression (14)(15)(16)(17).…”

Heme: a versatile signaling molecule controlling the activities of diverse regulators ranging from transcription factors to MAP kinases

“…Loss of function mutations in the IRR gene are sufficient to uncouple heme synthesis from iron availability, resulting in porphyrin accumulation and cytotoxicity [21,42,45]. Notably, recent findings indicate that in B. japonicum, IRR allows the sensing of iron level via heme synthesis to regulate iron homeostasis and metabolism [49]. In addition, it was also shown that IRR plays a role in mediating the control of heme synthesis in response to oxidative stress [50].…”