Regulation of iron homeostasis by Fur and atypical response regulator SsoR via derepressor-inhibitor oscillation in Shewanella oneidensis.

Abstract

Iron is a vital cofactor for enzymes essential to many biological processes, yet in excess, it poses a danger to all living organisms. In order to ensure survival and proliferation under fluctuating environmental iron levels, bacteria evolve sophisticated regulatory systems to maintain iron homeostasis. Unlike master regulator Fur, a large portion of other players remains poorly defined. Here, we characterized the physiological impacts of atypical phosphorylation-independent response regulator SsoR of Shewanella oneidensis, a γ-proteobacterium renowned for metabolic versatility. By combining transcriptomics, proteomics, and transposon screening, we discovered that the SsoR loss impairs growth and decreases cytochrome c content under iron-limited conditions. Further investigations revealed that the defects can be attributed to lowered heme and iron levels, a consequence of elevated Fur production. Together, our findings suggest that SsoR and Fur constitute a derepressing-inhibiting oscillation system in maintaining iron homeostasis, providing a new composite view of regulator dynamics during the regulation of iron homeostasis in bacteria.IMPORTANCEShewanella comprises a large group of bacteria that are ubiquitous, ecologically widespread, and metabolically versatile, having enormous potential in biotechnology, environmental remediation, and energy production. These characteristics and applications are crucially determined by a myriad of iron-containing proteins, whose activity depends on the intricate regulation of iron homeostasis. Our study reveals that a derepressing-inhibiting oscillation system composed of Fur and atypical phosphorylation-independent response regulator SsoR plays a key role in the regulation of iron homeostasis at the transcription level. The loss of either results in altered production of the other, leading to disruption of iron homeostasis, which is harmful to the cell, especially under iron-limited conditions. This study deepens our understanding of the interacting dynamics of multiple regulators in iron homeostasis.