Helicobacter pylori apo-Fur regulation appears unconserved across species

Abstract

The Ferric Uptake Regulator (Fur) is a transcriptional regulator that is conserved across a broad number of bacterial species and has been shown to regulate expression of iron uptake and storage genes. Additionally, Fur has been shown to be an important colonization factor of the gastric pathogen Helicobacter pylori. In H. pylori, Fur-dependent regulation appears to be unique in that Fur is able to act as a transcriptional repressor when bound to iron as well as in its iron free (apo) form. To date, apo-regulation has not been identified in any other bacterium. To determine whether Fur from other species has the capacity for apo-regulation, we investigated the ability of Fur from Escherichia coli, Campylobacter jejuni, Desulfovibrio vulgaris Hildenborough, Pseudomonas aeruginosa, and Vibrio cholerae to complement both iron-bound and apo-Fur regulation within the context of an H. pylori fur mutant. We found that while some Fur species (E. coli, C. jejuni and V. cholerae) complemented iron-bound regulation, apo-regulation was unable to be complemented by any of the examined species. These data suggest that despite the conservation among bacterial Fur proteins, H. pylori Fur contains unique structure/function features that make it novel in comparison to Fur from other species.

Structure and regulon of Campylobacter jejuni ferric uptake regulator Fur define apo-Fur regulation

“…Moreover, the crystal structure of HpFur failed to provide structural insights into apo-HpFur function, and previous work has suggested that the structure of CjFur differed from other Fur-family proteins (33). Because our results indicate that CjFur recognizes divergent DNA consensus sequences and regulates gene expression independently of iron, we reasoned that CjFur must possess unique structural features that have not yet been described for the Fur family of proteins.…”

Cysteine Mutational Studies Provide Insight into a Thiol-Based Redox Switch Mechanism of Metal and DNA Binding in FurA fromAnabaenasp. PCC 7120

“…In this sense, Fur participates in gene activation and iron-independent regulation of a variety of genes involved in distinct functions (6,36).…”

Fur-Mediated Global Regulatory Circuits in Pathogenic Neisseria Species

“…2B). apo-Fur repression has been primarily characterized in H. pylori and has not yet been well described in other bacteria (13,72). Although iron may not be important for apo-Fur function, it is possible that other metal ions play a role in apo-Fur-mediated transcriptional control (24,74,91).…”

“…Similar to N. meningitidis, gonococcal Furrepressed genes include a large number involved in iron acquisition (Table 2). However, only three genes or loci encoding proteins for energy metabolism and biosynthesis (fumC, NGO0108, and NGO0114) are identified as being Fur repressed in N. gonor- (13,72). (C) In the apo-Fur activation mechanism, Fur does not bind to the promoter region; thus, gene transcription is not active when iron is present (left panel).…”