Citrate-mediated iron uptake in Pseudomonas aeruginosa: involvement of the citrate-inducible FecA receptor and the FeoB ferrous iron transporter

Marshall, Bryan E.; Stintzi, Alain; Gilmour, C. M.; Meyer, Jean‐Marie; Poole, Keith

doi:10.1099/mic.0.023531-0

Cited by 89 publications

(102 citation statements)

References 68 publications

Supporting

Mentioning

100

Contrasting

Order By: Relevance

“…This suggested that our two-component system, comprising a cytoplasmic response regulator (bqsR) and a sensor histidine kinase (bqsS) and identified by its conserved kinase domain and its predicted localization to the inner membrane, was sensing extracellular Fe(II). To test this, we used qRT-PCR to measure the expression of bqsR and bqsS in response to Fe(II) shock in the wild-type (WT) strain and in strain feoB::MAR2xT7 [which has a severe defect in Fe(II) uptake across the cytoplasmic membrane (31,32,61)]. If the cells were sensing extracellular Fe(II), we anticipated that bqsR and bqsS expression would be the same in both the wild type and the feoB mutant.…”

Section: Resultsmentioning

confidence: 99%

“…When pyoverdine-bound Fe(III) enters the periplasm via TonB-dependent outer membrane transporters, iron is thought to be released from the pyoverdine complex via reduction facilitated by its binding to an inner membrane ABC transporter, allowing Fe(II) to enter the cytoplasm (59). In addition, P. aeruginosa can excrete citrate, which also chelates Fe(III), albeit with lower affinity than siderophores, causing the iron to enter the cytoplasm as Fe(II) through a different TonB-dependent porin and the G-protein-like transporter FeoB (31,32). Pseudomonas also contains two heme uptake systems whose outer membrane receptors are HasR and PhuR, which are energized by an ABC transporter and TonB, respectively (39).…”

mentioning

confidence: 99%

See 1 more Smart Citation

BqsR/BqsS Constitute a Two-Component System That Senses Extracellular Fe(II) in Pseudomonas aeruginosa

Kreamer¹,

Wilks²,

Marlow³

et al. 2011

Journal of Bacteriology

View full text Add to dashboard Cite

Pseudomonas aeruginosa is a ubiquitous Gram-negative bacterium best known as the predominant opportunistic pathogen infecting the lungs of cystic fibrosis patients. In this context, it is thought to form biofilms, within which locally reducing and acidic conditions can develop that favor the stability of ferrous iron [Fe(II)]. Because iron is a signal that stimulates biofilm formation, we performed a microarray study to determine whether P. aeruginosa strain PA14 exhibits a specific transcriptional response to extracellular Fe(II). Among the genes that were most upregulated in response to Fe(II) were those encoding the twocomponent system BqsR/BqsS, previously identified for its role in P. aeruginosa strain PAO1 biofilm decay (13)

show abstract

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

BqsR/BqsS Constitute a Two-Component System That Senses Extracellular Fe(II) in Pseudomonas aeruginosa

Kreamer¹,

Wilks²,

Marlow³

et al. 2011

Journal of Bacteriology

View full text Add to dashboard Cite

show abstract

“…In support of this idea, genes encoding the ferrous iron and heme uptake systems are consistently expressed by P. aeruginosa growing in the CF lung (33,35). P. aeruginosa acquires ferrous iron via the Feo system, a G-protein-like transporter of ferrous iron (36)(37)(38)(39), and mediates heme acquisition via at least two systems: Phu (Pseudomonas heme uptake) and Has (heme assimilation system) (40). Once internalized, heme is bound by the cytoplasmic heme chaperone PhuS and delivered to an iron-regulated heme oxygenase (hemO), which degrades heme to iron, CO, and biliverdin (BVIX) (41).…”

mentioning

confidence: 90%

Adaptation of Iron Homeostasis Pathways by a Pseudomonas aeruginosa Pyoverdine Mutant in the Cystic Fibrosis Lung

et al. 2014

View full text Add to dashboard Cite

c Cystic fibrosis (CF) patients suffer from chronic bacterial lung infections, most notably by Pseudomonas aeruginosa, which persists for decades in the lungs and undergoes extensive evolution. P. aeruginosa requires iron for virulence and uses the fluorescent siderophore pyoverdine to scavenge and solubilize ferric iron during acute infections. Pyoverdine mutants accumulate in the lungs of some CF patients, however, suggesting that the heme and ferrous iron acquisition pathways of P. aeruginosa are more important in this environment. Here, we sought to determine how evolution of P. aeruginosa in the CF lung affects iron acquisition and regulatory pathways through the use of longitudinal CF isolates. These analyses demonstrated a significant reduction of siderophore production during the course of CF lung infection in nearly all strains tested. Mass spectrometry analysis of one of these strains showed that the later CF isolate has streamlined the metabolic flux of extracellular heme through the HemO heme oxygenase, resulting in more-efficient heme utilization. Moreover, gene expression analysis shows that iron regulation via the PrrF small RNAs (sRNAs) is enhanced in the later CF isolate. Finally, analysis of P. aeruginosa gene expression in the lungs of various CF patients demonstrates that both PrrF and HemO are consistently expressed in the CF lung environment. Combined, these results suggest that heme is a critical source of iron during prolonged infection of the CF lung and that changes in iron and heme regulatory pathways play a crucial role in adaptation of P. aeruginosa to this ever-changing host environment.

show abstract

“…Ϫ mutant allowed for identification of the FecA outer membrane transporter and its role in citrate-mediated iron import (40), and high-affinity import of iron(III) dicitrate through FecA is well established in Escherichia coli and several other bacteria (7). As the DC3000 genome contains a fecA homolog (PSPTO_1207), DC3000 might pirate iron(III) dicitrate from host fluids.…”

Section: Pvdmentioning

confidence: 99%

The Phytopathogen Pseudomonas syringae pv. tomato DC3000 Has Three High-Affinity Iron-Scavenging Systems Functional under Iron Limitation Conditions but Dispensable for Pathogenesis

Jones

Wildermuth

2011

J Bacteriol

View full text Add to dashboard Cite

High-affinity iron scavenging through the use of siderophores is a well-established virulence determinant in mammalian pathogenesis. However, few examples have been reported for plant pathogens. Here, we use a genetic approach to investigate the role of siderophores in Pseudomonas syringae pv. tomato DC3000 (DC3000) virulence in tomato. DC3000, an agronomically important pathogen, has two known siderophores for highaffinity iron scavenging, yersiniabactin and pyoverdin, and we uncover a third siderophore, citrate, required for growth when iron is limiting. Though growth of a DC3000 triple mutant unable to either synthesize or import these siderophores is severely restricted in iron-limited culture, it is fully pathogenic. One explanation for this phenotype is that the DC3000 triple mutant is able to directly pirate plant iron compounds such as heme/hemin or iron-nicotianamine, and our data indicate that DC3000 can import iron-nicotianamine with high affinity. However, an alternative explanation, supported by data from others, is that the pathogenic environment of DC3000 (i.e., leaf apoplast) is not iron limited but is iron replete, with available iron of >1 M. Growth of the triple mutant in culture is restored to wild-type levels by supplementation with a variety of iron chelates at >1 M, including iron(III) dicitrate, a dominant chelate of the leaf apoplast. This suggests that lower-affinity iron import would be sufficient for DC3000 iron nutrition in planta and is in sharp contrast to the high-affinity iron-scavenging mechanisms required in mammalian pathogenesis.Pathogenic microorganisms must acquire all critical nutrients from the host environment in order to survive. Iron nutrition in particular presents a fundamental challenge due to its extremely low solubility in aerobic environments at moderate pHs (ϳ10 Ϫ9 M) and further host limitation of available free iron (e.g., ϳ10Ϫ18 M in mammalian fluids [22,44]). Most bacteria require much higher levels (i.e., 10 Ϫ6 to 10 Ϫ7 M of bioavailable iron) for optimal growth (24) and therefore must solve an iron supply problem for survival. There is abundant evidence that competition for iron is a key virulence determinant in mammalian pathosystems. Iron in human serum is predominantly complexed with transferrin protein (pFe ϭ 10 22 M [1]) and is therefore limited from invading pathogens. The human immune system can limit iron further through release of the iron-binding protein lactoferrin at the site of infection (57). Evading these defenses, several mammalian pathogens pirate host-synthesized heme for iron nutrition directly from host fluids (20). Alternatively, pathogenic bacteria can scavenge iron from host fluids using very high-affinity iron carriers termed siderophores that can effectively compete with host iron chelates for iron. Siderophores are low-molecular-weight compounds that are synthesized, exported from the bacterial cell, and then imported once bound to iron (43). As this strategy carries metabolic costs associated with siderophore synthesis and transp...

show abstract

Citrate-mediated iron uptake in Pseudomonas aeruginosa: involvement of the citrate-inducible FecA receptor and the FeoB ferrous iron transporter

Cited by 89 publications

References 68 publications

BqsR/BqsS Constitute a Two-Component System That Senses Extracellular Fe(II) in Pseudomonas aeruginosa

BqsR/BqsS Constitute a Two-Component System That Senses Extracellular Fe(II) in Pseudomonas aeruginosa

Adaptation of Iron Homeostasis Pathways by a Pseudomonas aeruginosa Pyoverdine Mutant in the Cystic Fibrosis Lung

The Phytopathogen Pseudomonas syringae pv. tomato DC3000 Has Three High-Affinity Iron-Scavenging Systems Functional under Iron Limitation Conditions but Dispensable for Pathogenesis

Contact Info

Product

Resources

About