Iron and Fur Regulation in Vibrio cholerae and the Role of Fur in Virulence

Abstract

Regulation of iron uptake and utilization is critical for bacterial growth and for prevention of iron toxicity. In many bacterial species, this regulation depends on the iron-responsive master regulator Fur. In this study we report the effects of iron and Fur on gene expression in Vibrio cholerae. We show that Fur has both positive and negative regulatory functions, and we demonstrate Fur-independent regulation of gene expression by iron. Nearly all of the known iron acquisition genes were repressed by Fur under iron-replete conditions. In addition, genes for two newly identified iron transport systems, Feo and Fbp, were found to be negatively regulated by iron and Fur. Other genes identified in this study as being induced in low iron and in the fur mutant include those encoding superoxide dismutase (sodA), fumarate dehydratase (fumC), bacterioferritin (bfr), bacterioferritin-associated ferredoxin (bfd), and multiple genes of unknown function. Several genes encoding ironcontaining proteins were repressed in low iron and in the fur mutant, possibly reflecting the need to reserve available iron for the most critical functions. Also repressed in the fur mutant, but independently of iron, were genes located in the V. cholerae pathogenicity island, encoding the toxin-coregulated pilus (TCP), and genes within the V. cholerae mega-integron. The fur mutant exhibited very weak autoagglutination, indicating a possible defect in expression or assembly of the TCP, a major virulence factor of V. cholerae. Consistent with this observation, the fur mutant competed poorly with its wild-type parental strain for colonization of the infant mouse gut.

A Comparative Analysis of Perturbations Caused by a Gene Knock-out, a Dominant Negative Allele, and a Set of Peptide Aptamers

“…Virulence Assay in Animals-Fur has been shown to play an important role in the virulence of different pathogenic bacteria (18,38). We thus set out to determine whether Fur90 and the Fur-binding peptide aptamers affected the virulence of a pathogenic E. coli strain in an in vivo model system.…”

“…About 100 genes from various E. coli strains have been shown to be regulated by Fur: most are involved in iron homeostasis; others act in metabolism and oxidative, nitrosative, and acidic stress responses (14 -17). Because fur deletion mutants of different pathogenic bacteria such as Vibrio cholerae (18) and Pseudomonas aeruginosa (19) show a decreased virulence, Fur is considered as a potential target for novel antibiotic therapies. Finally Fur has been extensively studied through the use of fur Ϫ strains, reporter genes, and fur mutants such as fur90 (H90Y) and fur51 (G51D), which were shown to negatively complement wild type fur (20).…”

Mapping the regulon of Vibrio cholerae ferric uptake regulator expands its known network of gene regulation

“…Expression profiles of bacteria lacking transcriptional regulators have been used successfully to broadly define genes impacted by the deleted regulator (1)(2)(3)(4). Although providing informative data, transcriptional analysis alone cannot distinguish between direct and indirect regulatory effects or identify regulated genes that may be transcriptionally silent under the test conditions.…”

Global transcriptional analysis of Mycoplasma hyopneumoniae following exposure to hydrogen peroxide

“…In Helicobacter pylori NapA plays a dual role in pathogenesis: in colonization and in protection against oxidative damage (Wang et al, 2006). As a protein that binds iron, it may thus serve as a primitive siderophore for mycoplasmas, although in previous work, napA was not transcriptionally responsive to changes in iron concentration in M. hyopneumoniae (Madsen et al, 2006b) as has been shown in other bacterial pathogens (Mey et al, 2005). The regulation of this gene may be a clear example of a mechanism M. hyopneumoniae uses to resist the host immune response by not activating neutrophils and thus decreasing the amount of oxidative radicals.…”