Effect ofNeisseria meningitidisFur Mutations on Global Control of Gene Transcription

Abstract

The ferric uptake regulator Fur is a well-known iron-responsive repressor of gene transcription, which is used by many bacteria to respond to the low-iron environment that pathogens encounter during infection. In this study we used comparative transcriptome analysis to define the role of the Fur protein in the global control of gene transcription and iron regulation in Neisseria meningitidis. By using the Fur-null mutant and its complemented derivative, we identified 83 genes whose transcription is controlled by Fur. We report that Fur may control differential expression of these genes by binding directly to their promoters or through indirect mechanisms. In addition, mutation of the fur gene resulted in the induction of the heat shock response, and transcription of these genes does not respond to iron limitation. Furthermore, analysis of the iron starvation stimulon in the Fur-null mutant provided evidences of iron-responsive regulation that is independent of Fur. We began to dissect the regulatory networks of Fur and the heat shock (stress) response in N. meningitidis, and the observed interlink between the two circuits is discussed.

The Hfq-Dependent Small Noncoding RNA NrrF Directly Mediates Fur-Dependent Positive Regulation of Succinate Dehydrogenase in Neisseria meningitidis

“…We cannot exclude the possibility that other mRNAs are targets for the NrrF regulator; however, under the conditions of the present study the succinate dehydrogenase genes were the only Fur-induced genes whose regulation was significantly mediated by NrrF. In N. meningitidis, we have previously identified a subset of genes that are positively regulated by Fur and iron with no evidence for a direct interaction of Fur in their regulatory region, and therefore these are candidate genes for this type of indirect posttranscriptional riboregulation (4).…”

“…The Fur protein in Neisseria meningitidis has been implicated in direct activation and, at the norB promoter, it was shown to bind to upstream sequences, resulting in the activation of RNA transcription in vivo and in vitro (6,11,12). Microarray experiments with the Fur-null mutant indicated that Fur positively regulates 43 genes in N. meningitidis (4), and a subset of these showed no evidence for direct binding of Fur in their promoter regions. As such, it was hypothesized that a similar indirect mechanism via a small regulatory RNA may be present in meningococcus.…”

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

“…5A), thus confirming the identity of the samples, the proper expression of the transgenes, and the strong Fur basal activity under our experimental conditions. 75 of the 196 selected genes have already been identified in previous transcriptome studies as Fur-and/or iron-regulated genes in E. coli (17,42), Helicobacter pylori (38,(43)(44)(45), Neisseria meningitidis (46,47), Pseudomonas aeruginosa (48,49), Campylobacter jejuni (50), Shewanella oneidensis (51,52), and Pasteurella multicoda (53). Conversely we unveiled 121 genes that have not been reported by previous studies.…”

Post-genomics ofNeisseria meningitidis: an update

“…Gene expression of bacterial culGene expression of bacterial cultures supplemented with ferric nitrate and depleted of iron have been compared [45]. A recently available fur deletion mutant allowed Delany and colleagues to perform global analysis of differentially expressed genes in the presence or absence of Fur protein and in response to iron limitation [47]. This allowed the identification of target genes affected by the Fur transcriptional regulator, and to distinguish those genes that are regulated by iron in a Fur-independent manner and by Fur in an iron-independent manner.…”

“…Pathogens possess and coordinate cellular mechanisms for iron acquisition and homeostasis, many of which in Neisseria are under the control of the iron-responsive transcriptional regulator protein Fur (reviewed in [44]). To define the Fur regulon of N. meningitidis, many comparative transcriptomics studies have been carried out [24,[45][46][47]. Gene expression of bacterial culGene expression of bacterial cultures supplemented with ferric nitrate and depleted of iron have been compared [45].…”