Role of ferrichrome as a ferric ionophore in Ustilago sphaerogena

Emery, Thomas

doi:10.1021/bi00784a033

Cited by 160 publications

(76 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is assumed that this mechanism applies to most of the noncatecholate siderophores. However, to our knowledge, direct evidence of siderophore recycling was additionally shown only for the hydroxamate-type siderophores aerobactin in E. coli (8) and ferrochromes in P. aeruginosa (9), E. coli (10), and Ustilago sphaerogena (11).…”

mentioning

confidence: 72%

Self-poisoning of Mycobacterium tuberculosis by interrupting siderophore recycling

Jones

Wells

Madduri

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

101

106

View full text Add to dashboard Cite

Siderophores are small iron-binding molecules secreted by bacteria to scavenge iron. Mycobacterium tuberculosis (Mtb), the etiologic agent of tuberculosis, produces the siderophores mycobactin and carboxymycobactin. Complexes of the mycobacterial membrane proteins MmpS4 and MmpS5 with the transporters MmpL4 and MmpL5 are required for siderophore export and virulence in Mtb.Here we show that, surprisingly, mycobactin or carboxymycobactin did not rescue the low-iron growth defect of the export mutant but severely impaired growth. Exogenous siderophores were taken up by the export mutant, and siderophore-delivered iron was used, but the deferrated siderophores accumulated intracellularly, indicating a blockade of siderophore recycling. This hypothesis was confirmed by the observation that radiolabeled carboxymycobactin was taken up and secreted again by Mtb. Addition of iron salts to an Mtb siderophore biosynthesis mutant stimulated more growth in the presence of a limiting amount of siderophores than iron-loaded siderophores alone. Thus, recycling enables Mtb to acquire iron at lower metabolic cost because Mtb cannot use iron salts without siderophores. Exogenous siderophores were bactericidal for the export mutant in submicromolar quantities. High-resolution mass spectrometry revealed that endogenous carboxymycobactin also accumulated in the export mutant. Toxic siderophore accumulation is prevented by a drug that inhibits siderophore biosynthesis. Intracellular accumulation of siderophores was toxic despite the use of an alternative iron source such as hemin, suggesting an additional inhibitory mechanism independent of iron availability. This study indicates that targeting siderophore export/recycling would deliver a one-two punch to Mtb: restricting access to iron and causing toxic intracellular siderophore accumulation.

show abstract

mentioning

confidence: 72%

Self-poisoning of Mycobacterium tuberculosis by interrupting siderophore recycling

Jones

Wells

Madduri

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

101

106

View full text Add to dashboard Cite

show abstract

“…This result indicates that the transporter must recognize a structural difference in the Fc once it has bound iron. It has been reported that there is little conformational difference between Fe-and Ga-complexed hydroxamate siderophores (21). Both metals are bound in the trivalent state, although unlike Fe-Fc, Ga-Fc complexes cannot be reduced.…”

Section: Resultsmentioning

confidence: 99%

Identification of a Candida albicans Ferrichrome Transporter and Its Characterization by Expression inSaccharomyces cerevisiae

Ardon

Bussey²,

Philpott³

et al. 2001

Journal of Biological Chemistry

View full text Add to dashboard Cite

Saccharomyces cerevisiae can accumulate iron through the uptake of siderophore-iron. Siderophore-iron uptake can occur through the reduction of the complex and the subsequent uptake of iron by the high affinity iron transporter Fet3p/Ftr1p. Alternatively, specific siderophore transporters can take up the siderophore-iron complex. The pathogenic fungus Candida albicans can also take up siderophore-iron. Here we identify a C. albicans siderophore transporter, CaArn1p, and characterize its activity. CaARN1 is transcriptionally regulated in response to iron. Through expression studies in S. cerevisiae strains lacking endogenous siderophore transporters, we demonstrate that CaArn1p specifically mediates the uptake of ferrichrome-iron. Iron-ferrichrome and galliumferrichrome, but not desferri-ferrichrome, could competitively inhibit the uptake of iron from ferrichrome. Uptake of siderophore-iron resulting from expression of CaARN1 under the control of the MET25-promoter in S. cerevisiae was independent of the iron status of the cells and of Aft1p, the iron-sensing transcription factor. These studies demonstrate that the expression of CaArn1p is both necessary and sufficient for the nonreductive uptake of ferrichrome-iron and suggests that the transporter may be the only required component of the siderophore uptake system that is regulated by iron and Aft1p.

show abstract

“…The relative rate of iron uptake by the two systems depends, among other factors, on the nature of the siderophore, on its extracellular concentration and on the concentration of oxygen in the cell suspension (Emery, 1971(Emery, , 1983(Emery, , 1987Ecker & Emery, 1983). The system described here for S. cerevisiae differs on essentially two points.…”

Section: General Conclusionmentioning

confidence: 99%

Reductive and Non-reductive Mechanisms of Iron Assimilation by the Yeast Saccharomyces cerevisiae

1989

View full text Add to dashboard Cite

Role of ferrichrome as a ferric ionophore in Ustilago sphaerogena

Cited by 160 publications

References 17 publications

Self-poisoning of Mycobacterium tuberculosis by interrupting siderophore recycling

Self-poisoning of Mycobacterium tuberculosis by interrupting siderophore recycling

Identification of a Candida albicans Ferrichrome Transporter and Its Characterization by Expression inSaccharomyces cerevisiae

Reductive and Non-reductive Mechanisms of Iron Assimilation by the Yeast Saccharomyces cerevisiae

Contact Info

Product

Resources

About