A cell biological view of the siderophore pyochelin iron uptake pathway inPseudomonas aeruginosa

2014 ◽  
Vol 17 (1) ◽  
pp. 171-185 ◽  
Author(s):  
Olivier Cunrath ◽  
Véronique Gasser ◽  
Françoise Hoegy ◽  
Cornelia Reimmann ◽  
Laurent Guillon ◽  
...  
Keyword(s):  
Iron Uptake ◽  
Uptake Pathway ◽  
A Cell

scholarly journals Pyoverdine-Mediated Iron Uptake in Pseudomonas aeruginosa: the Tat System Is Required for PvdN but Not for FpvA Transport

2006 ◽  
Vol 188 (9) ◽  
pp. 3317-3323 ◽  
Author(s):  
Romé Voulhoux ◽  
Alain Filloux ◽  
Isabelle J. Schalk
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Outer Membrane ◽  
Iron Uptake ◽  
Cytoplasmic Membrane ◽  
Signal Sequence ◽  
Iron Release ◽  
Outer Membrane Receptor ◽  
Uptake Pathway ◽  
Uptake Process ◽  
Tat System

ABSTRACT Under iron-limiting conditions, Pseudomonas aeruginosa PAO1 secretes a fluorescent siderophore called pyoverdine (Pvd). After chelating iron, this ferric siderophore is transported back into the cells via the outer membrane receptor FpvA. The Pvd-dependent iron uptake pathway requires several essential genes involved in both the synthesis of Pvd and the uptake of ferric Pvd inside the cell. A previous study describing the global phenotype of a tat-deficient P. aeruginosa strain showed that the defect in Pvd-mediated iron uptake was due to the Tat-dependent export of proteins involved in Pvd biogenesis and ferric Pvd uptake (U. Ochsner, A. Snyder, A. I. Vasil, and M. L. Vasil, Proc. Natl. Acad. Sci. USA 99:8312-8317, 2002). Using biochemical and biophysical tools, we showed that despite its predicted Tat signal sequence, FpvA is correctly located in the outer membrane of a tat mutant and is fully functional for all steps of the iron uptake process (ferric Pvd uptake and recycling of Pvd on FpvA after iron release). However, in the tat mutant, no Pvd was produced. This suggested that a key element in the Pvd biogenesis pathway must be exported to the periplasm by the Tat pathway. We located PvdN, a still unknown but essential component in Pvd biogenesis, at the periplasmic side of the cytoplasmic membrane and showed that its export is Tat dependent. Our results further support the idea that a critical step of the Pvd biogenesis pathway involving PvdN occurs at the periplasmic side of the cytoplasmic membrane.

Ontogenic changes in lactoferrin receptor and DMT1 in mouse small intestine: implications for iron absorption during early lifeThis paper is one of a selection of papers published in this Special Issue, entitled 7th International Conference on Lactoferrin: Structure, Function, and Applications, and has undergone the Journal's usual peer review process.

2006 ◽  
Vol 84 (3) ◽  
pp. 337-344 ◽  
Author(s):  
Veronica Lopez ◽  
Yasushi A. Suzuki ◽  
Bo Lönnerdal
Keyword(s):  
Small Intestine ◽  
Early Life ◽  
Iron Uptake ◽  
Iron Transport ◽  
Iron Homeostasis ◽  
Apical Membrane ◽  
Transport Pathway ◽  
Divalent Metal Transporter 1 ◽  
Uptake Pathway ◽  
Lactoferrin Receptor

It has been proposed that lactoferrin receptor (LfR) may be involved in intestinal iron transport during early life. However, it is known that iron homeostasis is regulated by divalent metal transporter 1 (DMT1; Nramp2/DCT1) in the adult small intestine. To address the hypothesis that LfR may play a role as an alternative iron transport pathway during early life, we used immunohistochemistry (IHC) to examine the localization of mouse LfR (mLfR) and DMT1. In addition to studying the localization and abundance of LfR and DMT1 on the apical membrane, intestinal brush-border membrane vesicles (BBMV) were isolated during the first 3 postnatal weeks (postnatal day (PD) 0, 5, 10, and 20). We found that mLfR is expressed in fetal mice as early as gestational days (GD) 13.5, 15.5, and 18.5. A 34 kD band for mLfR was detected at PD 0 through PD 20 in total intestine homogenate. However, mLfR protein did not appear in the BBMV preparations until PD 5 and was highly expressed at PD 10. By IHC, DMT1 protein was minimally observed at PD 0 and PD 5, but by PD 10 DMT1 was predominantly localized in the apical membrane of the maturing intestine. BBMV fractionation revealed 50–120 kD protein bands for DMT1. In these BBMV preparations, the apical-membrane-associated 120 kD band for DMT1 increased in abundance with age. However, in the corresponding total homogenates, only the deglycosylated form of DMT1 (50 kD) was identified. These results indicate that DMT1 is mislocalized during late gestation, minimally expressed during early life, and predominantly expressed in its deglycosylated form until PD 20. The immunolocalization and abundant protein expression of mLfR suggest that accrual of iron from Lf may be the principal iron uptake pathway at this age. In conclusion, our findings support the notion that until the development-dependent expression of DMT1 in the intestine is induced, mLfR may serve as an alternative iron uptake pathway.

The PvdRT-OpmQ efflux pump controls the metal selectivity of the iron uptake pathway mediated by the siderophore pyoverdine in Pseudomonas aeruginosa

2011 ◽  
Vol 14 (7) ◽  
pp. 1696-1708 ◽  
Author(s):  
Mélissa Hannauer ◽  
Armelle Braud ◽  
Françoise Hoegy ◽  
Pascale Ronot ◽  
Anne Boos ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Iron Uptake ◽  
Efflux Pump ◽  
Uptake Pathway ◽  
Metal Selectivity

scholarly journals Phenotypic Adaptation of Pseudomonas aeruginosa in the Presence of Siderophore-Antibiotic Conjugates during Epithelial Cell Infection

2020 ◽  
Vol 8 (11) ◽  
pp. 1820
Author(s):  
Quentin Perraud ◽  
Paola Cantero ◽  
Mathilde Munier ◽  
Françoise Hoegy ◽  
Nicolas Zill ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Phenotypic Plasticity ◽  
Epithelial Cell ◽  
Iron Uptake ◽  
Iron Acquisition ◽  
Trojan Horse ◽  
Cell Infection ◽  
Uptake Pathway ◽  
Pathway Expression ◽  
Uptake Process

Iron acquisition pathways have often been considered to be gateways for the uptake of antibiotics into bacteria. Bacteria excrete chelators, called siderophores, to access iron. Antibiotic molecules can be covalently attached to siderophores for their transport into pathogens during the iron-uptake process. P. aeruginosa produces two siderophores and is also able to use many siderophores produced by other bacteria. We investigated the phenotypic plasticity of iron-uptake pathway expression in an epithelial cell infection assay in the presence of two different siderophore–antibiotic conjugates, one with a hydroxamate siderophore and the second with a tris-catechol. Proteomic and RT-qPCR approaches showed that P. aeruginosa was able to sense the presence of both compounds in its environment and adapt the expression of its iron uptake pathways to access iron via them. Moreover, the catechol-type siderophore–antibiotic was clearly more efficient in inducing the expression of its corresponding transporter than the hydroxamate compound when both were simultaneously present. In parallel, the expression of the proteins of the two iron uptake pathways using siderophores produced by P. aeruginosa was significantly repressed in the presence of both conjugates. Altogether, the data indicate that catechol-type siderophores are more promising vectors for antibiotic vectorization using a Trojan-horse strategy.

scholarly journals Ferrous Iron Uptake in Cryptococcus neoformans

1998 ◽  
Vol 66 (9) ◽  
pp. 4169-4175 ◽  
Author(s):  
Eric S. Jacobson ◽  
Asha Prasad Goodner ◽  
Karin J. Nyhus
Keyword(s):  
Cryptococcus Neoformans ◽  
Iron Uptake ◽  
Opportunistic Pathogen ◽  
Metabolic Energy ◽  
Yeast Cells ◽  
Ferric Reductase ◽  
High Affinity ◽  
Steep Rise ◽  
Uptake Pathway ◽  
Uptake Activity

ABSTRACT Previous studies have implicated ferric reduction in the iron uptake pathway of the opportunistic pathogen Cryptococcus neoformans. Here we studied iron uptake directly, using55Fe in the presence of reductants. Uptake was linear with respect to time and number of yeast cells. The plot of uptake versus concentration exhibited a steep rise up to about 1 μM, a plateau between 1 and 25 μM, and a second steep rise above 25 μM, consistent with high- and low-affinity uptake systems. AKm for high-affinity uptake was estimated to be 0.6 μM Fe(II); 1 μM was used for standardized uptake assays. At this concentration, the uptake rate was 110 ± 3 pmol/106 cells/h. Iron repletion (15 μM) and copper starvation drastically decreased high-affinity iron uptake. Incubation at 0°C or in the presence of 2 mM KCN abolished high-affinity iron uptake, suggesting that uptake requires metabolic energy. When exogenous reducing agents were not supplied and the culture was washed free of secreted reductants, uptake was reduced by 46%; the remaining uptake activity presumably was dependent upon the cell membrane ferric reductase. Further decreases in free Fe(II) levels achieved by trapping with bathophenanthroline disulfonate or reoxidizing with potassium nitrosodisulfonate reduced iron uptake very drastically, suggesting that it is the Fe(II) species which is transported by the high-affinity transporter. The uptake of Fe was stimulated two- to threefold by deferoxamine, but this increment could be abolished by copper starvation or inhibition of the ferric reductase by Pt, indicating that Fe solubilized by this molecule also entered the reductive iron uptake pathway.

scholarly journals Present and future of siderophore-based therapeutic and diagnostic approaches in infectious diseases

2019 ◽  
Vol 11 (2) ◽  
Author(s):  
Gilda Tonziello ◽  
Emanuela Caraffa ◽  
Biagio Pinchera ◽  
Guido Granata ◽  
Nicola Petrosillo
Keyword(s):  
Infectious Diseases ◽  
Iron Uptake ◽  
Protein Complexes ◽  
Specific Binding ◽  
Binding Protein ◽  
Research Progress ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Uptake Pathway ◽  
Diagnostic Approaches

Iron is an essential micronutrient required for the growth of almost all aerobic organisms; the iron uptake pathway in bacteria therefore represents a possible target for novel antimicrobials, including hybrids between antimicrobials and siderophores. Siderophores are low molecular weight iron chelators that bind to iron and are actively transported inside the cell through specific binding protein complexes. These binding protein complexes are present both in Gram negative bacteria, in their outer and inner membrane, and in Gram positive bacteria in their cytoplasmic membrane. Most bacteria have the ability to produce siderophores in order to survive in environments with limited concentrations of free iron, however some bacteria synthetize natural siderophore-antibiotic conjugates that exploit the siderophore-iron uptake pathway to deliver antibiotics into competing bacterial cells and gain a competitive advantage. This approach has been referred to as a Trojan Horse Strategy. To overcome the increasing global problem of antibiotic resistance in Gram negative bacteria, which often have reduced outer membrane permeability, siderophore-antibiotic hybrid conjugates have been synthetized in vitro. Cefiderocol is the first siderophore-antibiotic conjugate that progressed to late stage clinical development so far. In studies on murine models the iron-siderophore uptake pathway has been also exploited for diagnostic imaging of infectious diseases, in which labelled siderophores have been used as specific probes. The aim of this review is to describe the research progress in the field of siderophore-based therapeutic and diagnostic approaches in infectious diseases.

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