MliR, a novel MerR-like regulator of iron homeostasis, impacts metabolism, membrane remodeling, and cell adhesion in the marine Bacteroidetes Bizionia argentinensis

Abstract

The MerR family is a group of transcriptional activators with conserved N-terminal helix-turn-helix DNA binding domains and variable C-terminal effector binding regions. In most MerR proteins the effector binding domain (EBD) contains a cysteine center suited for metal binding and mediates the response to environmental stimuli, such as oxidative stress, heavy metals or antibiotics. We here present a novel transcriptional regulator classified in the MerR superfamily that lacks an EBD domain and has neither conserved metal binding sites nor cysteine residues. This regulator from the psychrotolerant bacteria Bizionia argentinensis JUB59 is involved in iron homeostasis and was named MliR (MerR-like iron responsive Regulator). In silico analysis revealed that homologs of the MliR protein are widely distributed among different bacterial species. Deletion of the mliR gene led to decreased cell growth, increased cell adhesion and filamentation. Genome-wide transcriptomic analysis showed that genes associated with iron homeostasis were downregulated in mliR-deletion mutant. Through nuclear magnetic resonance-based metabolomics, ICP-MS, fluorescence microscopy and biochemical analysis we evaluated metabolic and phenotypic changes associated with mliR deletion. This work provides the first evidence of a MerR-family regulator involved in iron homeostasis and contributes to expanding our current knowledge on relevant metabolic pathways and cell remodeling mechanisms underlying in the adaptive response to iron availability in bacteria.

Copper resistance in the cold: Genome analysis and characterisation of a PIB‐1 ATPase in Bizionia argentinensis

“…There are two MerR transcriptional regulators (G2EA47, G2E8Y3); they both have an HTH merR‐type domain in the N‐terminal region, but they do not have the copper‐binding site reported for E. coli CueR (Changela et al, 2003 ), so they may not be involved in the regulation of copper homeostasis. Indeed, recently, it was reported that one of these transcriptional regulators is involved in iron homeostasis (Pellizza et al, 2022 ). Three BlaI/MecI/CopY family transcriptional regulators with similarity to the transcriptional repressor CopY from Enterococcus hirae (Q47839) were found in the genome of B. argentinensis (G2EAK1, G2ED45 and G2EAI2), but none of them has conserved the CopY copper‐binding site.…”