The Fur regulon in anaerobically grown Salmonella enterica sv. Typhimurium: identification of new Fur targets

Abstract

BackgroundThe Ferric uptake regulator (Fur) is a transcriptional regulator that controls iron homeostasis in bacteria. Although the regulatory role of Fur in Escherichia coli is well characterized, most of the studies were conducted under routine culture conditions, i.e., in ambient oxygen concentration. To reveal potentially novel aspects of the Fur regulon in Salmonella enterica serovar Typhimurium under oxygen conditions similar to that encountered in the host, we compared the transcriptional profiles of the virulent wild-type strain (ATCC 14028s) and its isogenic Δfur strain under anaerobic conditions.ResultsMicroarray analysis of anaerobically grown Δfur S. Typhimurium identified 298 differentially expressed genes. Expression of several genes controlled by Fnr and NsrR appeared to be also dependent on Fur. Furthermore, Fur was required for the activity of the cytoplasmic superoxide disumutases (MnSOD and FeSOD). The regulation of FeSOD gene, sodB, occurred via small RNAs (i.e., the ryhB homologs, rfrA and rfrB) with the aid of the RNA chaperone Hfq. The transcription of sodA was increased in Δfur; however, the enzyme was inactive due to the incorporation of iron instead of manganese in SodA. Additionally, in Δfur, the expression of the gene coding for the ferritin-like protein (ftnB) was down-regulated, while the transcription of the gene coding for the nitric oxide (NO·) detoxifying flavohemoglobin (hmpA) was up-regulated. The promoters of ftnB and hmpA do not contain recognized Fur binding motifs, which indicated their probable indirect regulation by Fur. However, Fur activation of ftnB was independent of Fnr. In addition, the expression of the gene coding for the histone-like protein, H-NS (hns) was increased in Δfur. This may explain the observed down-regulation of the tdc operon, responsible for the anaerobic degradation of threonine, and ftnB in Δfur.ConclusionsThis study determined that Fur is a positive factor in ftnB regulation, while serving to repress the expression of hmpA. Furthermore, Fur is required for the proper expression and activation of the antioxidant enzymes, FeSOD and MnSOD. Finally, this work identified twenty-six new targets of Fur regulation, and demonstrates that H-NS repressed genes are down-regulated in Δfur.

Fur-Mediated Global Regulatory Circuits in Pathogenic Neisseria Species

“…Recently, global analyses of iron-and/or Fur-responsive transcriptomes of diverse bacterial pathogens, such as H. pylori, Pseudomonas syringae, Vibrio cholerae, Yersinia pestis, Haemophilus influenzae, S. enterica serovar Typhimurium, and Listeria monocytogenes, have revealed a number of novel regulatory roles for Fur (12,20,40,56,68,94,101,102,107). First, Fur has been demonstrated to repress transcription even in the absence of iron, a process termed apo-Fur regulation (13) (Fig.…”

Salmonella Pathogenicity and Host Adaptation in Chicken-Associated Serovars

“…(292). These include, in addition to specific host-generated immuneand non-immune-based defenses, iron limitation, acidic and pH shifts, oxidative and osmolarity stresses, and limited nutrient availability that leads to starvation (35,36,(293)(294)(295)(296)(297)(298)(299)(300)(301). Although these barriers are manifested either as a function of the host's defense mechanisms or as a consequence of high population densities and a metabolically active indigenous GIT microbial population, in reality, there is a substantial interaction between the two that makes it difficult to separate them experimentally.…”

Salmonella Utilizes D-Glucosaminate via a Mannose Family Phosphotransferase System Permease and Associated Enzymes

“…There have been numerous studies in which the Salmonella transcriptome has been analyzed by use of bacteria grown in vivo (e.g., during infection of macrophage-like cells or epithelial cells or isolated from the intestinal tract), cultured under different conditions, or exposed to various chemical stimuli (53)(54)(55)(56)(57)(58)(59)(60)(61). In addition, there are several reports on how the loss of known global regulators affects the Salmonella transcriptome (62)(63)(64). A recent study used proteomic, mutant phenotyping, and computational approaches to investigate Salmonella nutrition in a mouse typhoid fever model (65).…”