Iron and metal regulation in bacteria

Hantke, Klaus

doi:10.1016/s1369-5274(00)00184-3

Cited by 671 publications

(653 citation statements)

References 30 publications

Supporting

Mentioning

636

Contrasting

Unclassified

Order By: Relevance

“…7,10 Recent studies have shown that enzymatic functionalization of enterobactin makes water soluble derivatives that evade these traps. 11,12 At low pH ferric enterobactin is protonated, remains intact and undergoes a marked structural change.…”

Section: Resultsmentioning

confidence: 99%

“…Because the growth of pathogenic bacteria depends on adequate iron supply, iron metabolism is a key determinant in bacterial disease. [5][6][7][8][9] The recent discovery of siderocalin, a protein produced by the human immune system which sequesters and inactivates siderophores, has heightened this significance. 10 Functionalization to increase siderophore water solubility alters the iron transport capability in a host organism and also the pathogenicity of the producing organism.…”

Section: Introductionmentioning

confidence: 99%

“…13 The metabolism of this powerful iron chelator is tightly controlled by the Fur (Fe uptake regulation) protein. 7 Much is known about the biosynthesis and TolC-dependent exportation of the aposiderophore as well as the TonB-dependent FepA recognition of the enterobactin ferric complex. 3,4 The iron release mechanism from the ferric enterobactin complex to intracellular iron carriers occurs primarily through enzymatic hydrolysis of the siderophore trilactone backbone by the esterase Fes.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Enterobactin Protonation and Iron Release: Structural Characterization of the Salicylate Coordination Shift in Ferric Enterobactin¹

et al. 2006

View full text Add to dashboard Cite

The siderophore enterobactin (Ent) is produced by many species of enteric bacteria to mediate iron uptake. This iron scavenger can be reincorporated by the bacteria as the ferric complex [Fe III (Ent)] 3-and is subsequently hydrolyzed by an esterase to facilitate intracellular iron release. Recent literature reports on altered protein recognition and binding of modified enterobactin increase the significance of understanding the structural features and solution chemistry of ferric enterobactin. The structure of the neutral protonated ferric enterobactin complex [Fe III (H 3 (14) Å 2 ). 1 H NMR spectroscopy was used to monitor the amide bond rotation between the catecholate and salicylate geometries using the gallic complexes of enterobactin; [Ga III (Ent)] 3-and [Ga III (H 3 Ent)] 0 . The ferric salicylate complexes display quasi-reversible reduction potentials from −89 mV to −551 mV (relative to the normal hydrogen electrode NHE) which supports the feasibility of a low pH iron release mechanism facilitated by biological reductants. Keywords

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Enterobactin Protonation and Iron Release: Structural Characterization of the Salicylate Coordination Shift in Ferric Enterobactin¹

et al. 2006

View full text Add to dashboard Cite

show abstract

“…Therefore, Salmonella has evolved both siderophore-dependent and -independent mechanisms to acquire iron from intracellular host sources; on the one hand, S. typhimurium produces enterochelin and salmochelins via its enzymes entC and iroB, respectively, the latter encoded within the iroA gene cluster [16,17]. On the other hand, non-siderophorebound ferrous iron is taken up by Feo, a pathway that may be most relevant in microenvironments with low oxygen tension [18]. Of note, both siderophore-dependent and -independent mechanisms of iron uptake are linked to bacterial virulence [11,19,20].…”

Section: Introductionmentioning

confidence: 99%

Interferon‐γ limits the availability of iron for intramacrophage Salmonella typhimurium

et al. 2008

Self Cite

View full text Add to dashboard Cite

In stimulating effector functions of mononuclear phagocytes, IFN-c is of pivotal importance in host defense against intramacrophage pathogens including salmonellae. As the activity of IFN-c is modulated by iron and since a sufficient availability of iron is essential for the growth of pathogens, we investigated the regulatory effects of IFN-c on iron homeostasis and immune function in murine macrophages infected with Salmonella typhimurium. In Salmonella-infected phagocytes, IFN-c caused a significant reduction of iron uptake via transferrin receptor 1 and resulted in an increased iron efflux caused by an enhanced expression of the iron exporter ferroportin 1. Moreover, the expression of haem oxygenase 1 and of the siderophore-capturing antimicrobial peptide lipocalin 2 was markedly elevated following bacterial invasion, with IFN-c exerting a super-inducing effect. This observed regulatory impact of IFN-c reduced the intracellular iron pools within infected phagocytes, thus restricting the acquisition of iron by engulfed Salmonella typhimurium while concomitantly promoting NO and TNF-a production. Our data suggest that the modulation of crucial pathways of macrophage iron metabolism in response to IFN-c concordantly aims at withdrawing iron from intracellular Salmonella and at strengthening macrophage immune response functions. These regulations are thus consistent with the principles of nutritional immunity. IntroductionHost defense against intracellular microbes such as salmonellae or mycobacteria strongly depends on cell-mediated immunity, a major component of which is characterized by interactions between Th1 cells and macrophages [1]. By secreting Th1 cytokines, particularly IFN-c, antigen-specific Th1 cells activate a plethora of microbicidal mechanisms in infected macrophages. Specifically, in mononuclear phagocytes infected with Salmonella enterica serovar typhimurium (S. typhimurium), IFN-c promotes the internalization of bacteria and stimulates their elimination by various mechanisms including reactive oxygen and nitrogen species (ROS and RNS), generated via NADPH phagocyte oxidase and iNOS, respectively [2][3][4][5]. In Salmonella-infected mice, treatment with recombinant IFN-c increases host survival and decreases bacterial numbers in liver and spleen [6]. Conversely, neutralization of murine IFN-c functions with specific antibodies results in reduced host survival and increased bacterial counts [7]. Eur. J. Immunol. 2008. 38: 1923-1936 Immunity to infection In humans, the central importance of IFN-c for immune response against salmonellae is highlighted by the fact that patients with genetic defects in the IL-12-induced production of IFN-c or in the IFN-c receptor 1 selectively suffer from infections with salmonellae and otherwise weakly pathogenic mycobacteria since their phagocytes fail to eliminate these microbes [8,9]. Iron serves as an essential nutrient for nearly all pathogenic microorganisms, and the expression of iron acquisition systems by infectious agents is associated with their virule...

show abstract

“…It seems very likely that the two transcriptional regulators encoded by ORF4 and ORF8 play an important role in transducing these environmental signals to the transcription apparatus, although this has not yet been established. To date two transcriptional repressors, Fur and IdeR, controlling iron dependent gene expression have been identified [31]. Although these proteins are unrelated, they operate in a similar manner.…”

Section: Regulation Of Virulence Plasmid Gene Expressionmentioning

confidence: 99%

Rhodococcus equi

2004

View full text Add to dashboard Cite

-Rhodococcus equi is an important cause of subacute or chronic abscessating bronchopneumonia of foals up to 3-5 months of age. It shares the lipid-rich cell wall envelope characteristic of the mycolata, including Mycobacterium tuberculosis, as well as the ability of pathogenic members of this group to survive within macrophages. The possession of a large virulence plasmid in isolates recovered from pneumonic foals is crucial for virulence. The plasmid contains an 27 kb pathogenicity island (PI) that encodes seven related virulence-associated proteins (Vaps), including the immunodominant surface-expressed protein, VapA. Only PI genes are differentially expressed when the organism is grown in macrophages in vitro. Ten of the PI genes, including six Vap genes, have signal sequences, suggesting that they are exported from the cell to interact with the macrophage. Different PI genes are regulated by temperature, pH, iron, oxidative stress and probably also by magnesium, all environmental changes encountered after environmental R. equi are inhaled in dust and are ingested into macrophages in the lung. The basis of pathogenicity of R. equi is its ability to multiply in and eventually to destroy alveolar macrophages. Infectivity is largely or exclusively limited to cells of the monocyte-macrophage lineage. Current evidence suggests that infection of foals with virulent R. equi results in some foals in subversion of cellmediated immunity and development of an ineffective and sometimes lethal Th2-based immune response. Significant progress has been made recently in the development of R. equi-E. coli shuttle vectors, transformation and random and site specific mutagenesis procedures, all of which will be important in molecular dissection of the mechanisms by which R. equi subverts normal macrophage killing mechanisms and cell-mediated immunity.

show abstract

Iron and metal regulation in bacteria

Cited by 671 publications

References 30 publications

Enterobactin Protonation and Iron Release: Structural Characterization of the Salicylate Coordination Shift in Ferric Enterobactin¹

Enterobactin Protonation and Iron Release: Structural Characterization of the Salicylate Coordination Shift in Ferric Enterobactin¹

Interferon‐γ limits the availability of iron for intramacrophage Salmonella typhimurium

Rhodococcus equi

Contact Info

Product

Resources

About

Iron and metal regulation in bacteria

Cited by 671 publications

References 30 publications

Enterobactin Protonation and Iron Release: Structural Characterization of the Salicylate Coordination Shift in Ferric Enterobactin1

Enterobactin Protonation and Iron Release: Structural Characterization of the Salicylate Coordination Shift in Ferric Enterobactin1

Interferon‐γ limits the availability of iron for intramacrophage Salmonella typhimurium

Rhodococcus equi

Contact Info

Product

Resources

About

Enterobactin Protonation and Iron Release: Structural Characterization of the Salicylate Coordination Shift in Ferric Enterobactin¹

Enterobactin Protonation and Iron Release: Structural Characterization of the Salicylate Coordination Shift in Ferric Enterobactin¹