The Burkholderia cenocepacia iron starvation σ factor, OrbS, possesses an on-board iron sensor. Issue 7 (2nd March 2022)

• Record Type: Journal Article
• Authors: Butt, Aaron T; Banyard, Christopher D; Haldipurkar, Sayali S; Agnoli, Kirsty; Mohsin, Muslim I; Vitovski, Srdjan; Paleja, Ameya; Tang, Yingzhi; Lomax, Rebecca; Ye, Fuzhou; Green, Jeffrey; Thomas, Mark S
• Is Part Of: Nucleic acids research. Volume 50:Issue 7(2022)
• Page Start: 3709
• Page End: 3726
• Publication Date: 2022-03-02
• Subjects: Nucleic acids -- Periodicals; Molecular biology -- Periodicals; 572.805
• DOI: 10.1093/nar/gkac137
• Languages: English
• ISSNs: 0305-1048

Abstract

Abstract: Burkholderia cenocepacia is an opportunistic pathogen that causes severe infections of the cystic fibrosis (CF) lung. To acquire iron, B. cenocepacia secretes the Fe(III)-binding compound, ornibactin. Genes for synthesis and utilisation of ornibactin are served by the iron starvation (IS) extracytoplasmic function (ECF) σ factor, OrbS. Transcription of orbS is regulated in response to the prevailing iron concentration by the ferric uptake regulator (Fur), such that orbS expression is repressed under iron-sufficient conditions. Here we show that, in addition to Fur-mediated regulation of orbS, the OrbS protein itself responds to intracellular iron availability. Substitution of cysteine residues in the C-terminal region of OrbS diminished the ability to respond to Fe(II) in vivo . Accordingly, whilst Fe(II) impaired transcription from and recognition of OrbS-dependent promoters in vitro by inhibiting the binding of OrbS to core RNA polymerase (RNAP), the cysteine-substituted OrbS variant was less responsive to Fe(II). Thus, the cysteine residues within the C-terminal region of OrbS contribute to an iron-sensing motif that serves as an on-board 'anti-σ factor' in the presence of Fe(II). A model to account for the presence two regulators (Fur and OrbS) that respond to the same intracellular Fe(II) signal to control ornibactin synthesis and utilisation is discussed. Graphical Abstract: