IMR Press / FBL / Volume 25 / Issue 4 / DOI: 10.2741/4827
Open Access Article
Iron should be restricted in acute infection
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1 Department of Psychology and Neuroscience, Dalhousie University, Halifax, Canada
2 Department of Microbiology and Immunology, Dalhousie University, Halifax, Canada
3 Department of Anesthesia, Pain Management and Perioperative Medicine, Dalhousie University, Halifax, Canada
4 Department of Pharmacology, Dalhousie University, Halifax, Canada
5 Department of Physiology and Biophysics, Dalhousie University, Halifax, Canada
Front. Biosci. (Landmark Ed) 2020, 25(4), 673–682;
Published: 1 January 2020
(This article belongs to the Special Issue Pro and con iron and ROS in inflammation and infection)

The trace element iron plays important roles in biological systems. Vital functions of both host organisms and pathogens require iron. During infection, the innate immune system reduces iron availability for invading organisms. Pathogens acquire iron through different mechanisms, primarily through the secretion of high-affinity iron chelating compounds known as siderophores. Bacterial siderophores have been used clinically for iron chelation, however synthetic iron chelators are superior for treating infection because - in contrast to siderophore-bound iron - bacteria are not able to utilize iron bound to those molecules. Additionally, utilizing siderophores-dependent iron uptake in a “trojan horse” manner represents a potential option to carry antibiotics into bacterial cells. Recently, synthetic iron chelators have been shown to enhance antibiotic effectiveness and overcome antibiotic resistance. This has implications for the treatment of infections through combination therapy of iron chelators and antibiotics.

Acute Infection

Iron plays important roles in biological systems as a co-factor in multiple cellular pathways including: DNA synthesis and repair, electron transfer, oxygen transport and immune response (1–4). Iron exists in the 2+ (ferrous) as well as the 3+ (ferric) valence state and is absorbed by duodenal enterocytes through active, enzymatic processes, e.g. by divalent metal transporter 1 (DMT1). Iron is exported into the plasma by the iron exporter ferroportin (5). In the plasma, ferric iron is bound to transferrin in order to circulate to sites of use (6). The majority of iron is used in erythropoiesis. Erythroid precursors express cell-surface transferrin receptors, which act to take up iron by receptor mediated endocytosis (7). Finally, 65-75% of iron in the body is contained within the protoporphyrin ring of heme, associated with hemoglobin (8). Excess iron can be stored in enterocytes, hepatocytes, macrophages and other cells by binding to ferritin (9). Macrophages are able to recycle iron by phagocytosis of aged or damaged erythrocytes. In healthy individuals, the availability of free iron is limited by tight regulation of absorption, recycling and intracellular storage. Hepcidin, a peptide hormone secreted by the liver, has been shown to regulate iron homoeostasis by binding to ferroportin causing it’s internalization and degradation, preventing extracellular iron efflux (10). Transferrin receptor 1 and bone morphogenetic protein 6 receptor are able to sense transferrin saturation and tissue iron content. This allows for regulation of hepcidin expression, communicating a need for more or less iron (11).

Iron also catalyzes the production of reactive oxygen species (ROS) such as highly reactive hydroxyl radicals from the association of superoxide and hydrogen peroxide, commonly known as the Haber-Weiss reaction. The generation of ROS is one of the first responses of immune cells to an infection in order to destroy invading microbes (12). However, overproduction of ROS can lead to adverse effects on host cells by damaging DNA, lipids and proteins (13). In response to infection, the body reduces the availability of iron in both the extracellular and intracellular space. This host defense mechanism blocks iron availability for invading microorganisms, restricting their ability to proliferate and is mediated by hepcidin. In infection, increased hepcidin synthesis is induced by inflammatory mediators, such as interleukin (IL)-6 and IL-22 (10, 14, 15). Other proinflammatory stimuli such as tumor necrosis factor α (TNF-α) and interferon-γ have been linked to the upregulation of DMT1 expression, resulting in an increased uptake of iron into macrophages (16). Furthermore, IL-4, IL-10 and IL-13 increase the expression of ferritin, promoting iron storage within monocytes and macrophages (17). In summary, all of these pathophysiological mechanisms of iron retention appear to be beneficial in fighting infections by reducing levels of available iron for microbes.

3.1. Learning from microbes

Pathogens have developed various strategies to acquire iron. The majority of bacteria and fungi utilize high-affinity chelating compounds to bind iron, so called siderophores. This area has been extensively studied and hundreds of siderophores have been discovered. Siderophores are classified into three main structural families, carboxylates, catecholates and hydroxamates (18). Catecholate siderophores have the highest affinity for ferric iron relative to carboxylate and hydroxamate siderophores under physiological conditions. Enterobactin, a catecholate siderophore, exhibits the highest known affinity for ferric iron, higher than that of the host iron binding protein transferrin (18). Hydroxamate siderophores are the most common group of siderophores in nature (19). Some siderophores from bacteria are used clinically for iron chelation. Desferrioxamine (DFO) is a clinically approved iron chelator originating from Streptomyces pilosus (20). DFO has three bidentate hydroxamic acid groups along the DFO backbone. The chain-like molecules wrap around iron in a 1:1 Fe (3+)/DFO complex manner (21). DFO has been used clinically to mobilize excess iron to excretion in patients with hemochromatosis and beta-thalassemia (22). However, DFO is not ideal as an iron chelator in bacterial infections as many bacterial species are able to utilize the iron sequestered within DFO (23). Growth of Microbacterium spp. has been shown to essentially require DFO while the growth of other bacteria (e.g., Gordonia,Paenibacillus and Burkholderia) is significantly promoted by DFO presence (24).

3.2. Restricting iron with synthetic iron chelators

Synthetic iron chelators typically contain oxygen, nitrogen or sulfur-donor atoms that form bonds with iron. They are chemical diverse, allowing for different binding capacities and preference for ferric or ferrous iron. In order to be used therapeutically, chelators must successfully compete with biological iron binding substances. Although DFO has been shown to effectively treat iron overload, it requires prolonged infusions five to seven days per week. Research has therefore focused on developing superior, synthetic iron chelators. A summary of different iron chelator properties can be found in Table 1 (25).

Table 1 Overview of selected iron chelators
Properties Deferoxamine Deferiprone Deferasirox
Binding capacity (chelator:iron) Hexadentate (1:1) Tridentate (3:1) Bidentate (2:1)
Route of administration Subcutaneous, intravenous Oral tablet Oral tablet
Side Effects Local skin reaction Ophthalmological Auditory Allergic reaction Growth retardation Neurological at high doses Pulmonary at high doses Agranulocytosis Musculoskeletal and joint pains Gastrointestinal Zinc deficiency Gastrointestinal Rash Rise in creatinine Ophthalmological Auditory
Half-life 47-134 minutes 3-4 hours 8-16 hours
Based on (27)

Deferiprone (Ferriprox®; DFP) is an FDA-approved oral iron chelator. DFP has comparable efficacy to DFO but is more effective in removing iron from the heart. It has a plasma half-life of 47-134 minutes and should therefore be taken three times daily. Major toxic side effects of DFP include agranulocytosis, musculoskeletal and joint pains, gastric intolerance, and zinc deficiency. However, these are considered to be reversible (26).

Deferasirox (Exjade®; DFX) is an FDA-approved oral iron chelator with similar efficacy to that of DFO in reducing liver iron levels. DFX has a plasma half-life of 8 to 16 hours and should therefore be taken once daily. Gastrointestinal disturbances are the most common side effect of DFX but can be improved by changing time of DFX administration. Rare reports of hepatic failure and serum creatinine increase have led to the suggestion that liver and kidney function should be monitored monthly (27).

Iron withholding is a host defense mechanism against invading pathogens. Synthetic iron chelation intensifies the host defense strategy, possessing antimicrobial potential. Recent studies suggest a potential role for iron chelators in treating infection. The impact of a novel iron chelator, DIBI, on bacterial proliferation in a murine model of sepsis found a significant decrease in bacterial counts in blood and peritoneal lavage fluid (PLF) when DIBI was used in combination with imipenem (28). Iron chelators have also been shown as an effective therapy against biofilms formed by Pseudomonas aeruginosa. The combination of DFO or deferasirox (DFX) with tobramycin reduced established biofilms and viable bacteria, as well as prevented the formation of new biofilm on cystic fibrosis airway cells (29). Lastly, combination therapy of DFX and vancomycin was shown to reduce viability of methicillin-resistant and vancomycin-intermediate strains of Staphylococcus aureus in vitro (30).

3.3. Other bacterial strategies for iron acquisition as drug target for new antibiotics

Further strategies for iron acquisition have been extensively studied in Gram-negative bacteria, few examples are known in regard to Gram-positive bacteria (31). Several pathogenic bacteria secrete hemolysins to lyse erythrocytes, and hemoglobin proteases to degrade the protein (32). The expression of hemolysins and other virulence factors is under control of the accessory gene regulatory (Agr) quorum-sensing two-component system (33). The small molecule savarin has been shown to alter binding of Agr to DNA and thereby prevent virulence gene upregulation. Studies by Sully et al. found savarin to be an effective treatment in murine S. aureus skin infection models by inhibiting Agr quorum sensing (34).

Gram-negative pathogens are able to uptake heme directly through TonB-dependent outer membrane (OM) receptors. Transport through the periplasmic and inner membrane is then facilitated by ABC transport system. Once in the cytoplasm heme is degraded and the iron is stored (31). Gram-negative bacteria are also able to acquire iron through the secretion of hemophores which have the ability to bind heme and heme-containing proteins. These hemophores then deliver heme to OM receptors (e.g., HasR) which allow heme to be internalized (35). Pseudomonas aeruginosa acquires heme via the hemophore, heme acquisition system A (HasA) protein. Studies by Shirataki et al. showed the crystal structure of the heme-loaded HasA and concluded that other metal complexes could also fit within the binding site. This knowledge allowed them to use Fe-phthalocyanine (Fe-Pc), a synthetic metal complex, to bind HasA and inhibit growth of P. aeruginosa, even in the presence of heme-bound HasA (36).

In Gram-positive bacteria, the iron regulated surface determinant (Isd) system of Staphylococcus aureus is a widely studied mechanism of iron acquisition from heme and hemoglobin. The Isd system consists of nine iron regulated proteins, IsdA, IsdB, IsdC, IsdH/HarA, IsdD/E/F, IsdG and IsdI. Together, these proteins interact with heme proteins to extract the heme molecule and internalize it into the cytoplasm of bacteria (37). Bacterial pathogens are also able to acquire iron through sources of iron such as transferrin, lactoferrin and ferritins through OM receptors that directly recognize these proteins. Neisseria utilizes transferrin-binding protein A (TbpA), a Ton-B dependent receptor, for the uptake of iron from human transferrin (38). It has been demonstrated that E. coli of intestinal origin is capable of using catecholamines in order to acquire iron from lactoferrin and transferrin, stimulating the growth of bacteria (39).

Bacteria utilize the ferric uptake regulator (Fur) family of transcriptional activators in order to control iron metabolism (40). Fur is a DNA-binding repressor that uses ferrous iron as a co-factor. Under normal iron conditions Fur binds to promotor regions of iron-regulated gene to repress their expression. During iron starvation, the complex dissociates from DNA allowing transcription of iron-regulated genes (32). However, fur has a higher affinity for Zn2+. Consequently, studies by Klemm and colleagues impaired the fur system by treating urinary tract E. coli and K. pneumonia isolates with high levels of Zn2+. This created competition for fur and effectively reduced biofilm formation (41).

Bacteria with stronger iron acquisition strategies have a growth advantage. Klebsiella pneumoniae is known to cause a significant number of community-acquired (CA) infections. Studies by Holt et al. found isolates from CA invasive infections to have additional siderophore and iron-metabolism genes. They concluded this enhanced ability to sequester host iron allowing K. pneumoniae to cause disease in immunologically competent human hosts (42, 43). Targeting the nutritional immunity of invading microbes (i.e. iron metabolism) has been shown to have impact on virulence. Therefore, targeting the range of different proteins involved in bacterial iron uptake presents as a possible novel target for new antibiotics. However, uptake mechanisms and proteins vary across pathogens. This requires a therapy with a carefully chosen target protein or pathway, in contrast to a broad-range treatment which may not be suitable.

3.4. Siderophores as gates for antibiotics

Bacterial structure plays a key role in antibiotic resistance. The bacterial envelope, consisting of an inner and outer membrane, decreases antibiotic penetration. Utilizing siderophore-dependent iron uptake in a “Trojan horse” manner has been used as a strategy to circumvent this barrier. This strategy assembles the siderophore, linker and antibiotic into one conjugate in order for the bacteria to attempt to make use of the siderophore and in doing so, transport the antibiotic across the outer membrane. Most conjugates are unable to be transported across the inner membrane, therefore the most successful utilize antibiotics with periplasmic targets (44). Siderophore-antibiotic conjugates have been developed for use against Pseudomonas aeruginosa. Budzikiewicz and colleagues conjugated PVD to ampicillin and tested its activity against P. aeruginosa. The conjugate had high levels of antibacterial activity against ampicillin resistant strains. When conjugated with PVD, ampicillin was able to utilize the iron-uptake pathway in order to reach its target in the periplasm and inhibit synthesis of the peptidoglycan (45).

3.5. Iron chelation overcomes antibiotic resistances

The rapid appearance of antibiotic resistance is termed by the Centers for Disease Control and Prevention (CDC) as a global crisis requiring the development of new antibiotics and novel approaches to the treatment of infections (46, 47). Recent evidence suggests iron chelators as potential treatment to overcome antibiotic resistances in both fungi and bacteria. Growth of Candida albicans, an opportunistic pathogen with developing resistance to antifungals, has been shown to be inhibited when treated with DIBI at low concentrations and in combination with fluconazole (FLC) in vitro. Furthermore, combination treatment of DIBI/FLC resulted in total growth inhibition in vitro of FLC resistant C. albicans strain LP1158-07, demonstrating the ability of iron chelation to overcome antibiotic resistance (48). The ability of iron chelators to overcome antibiotic resistance has also been shown in Acinetobacter baumannii, a major cause of hospital-acquired pneumonia. Mice infected with ciprofloxacin (CIP)-resistant A. baumannii strain LAC-4 were treated with CIP/DIBI combination in vivo. DIBI was found to improve the treatment efficacy of CIP and reduce bacterial burdens in the lung, spleen and blood. In addition, DIBI enhanced the efficacy of CIP for CIP-resistant LAC-4 isolates in vitro (23). Results of these studies demonstrate the potential of iron chelators to work in conjunction with antibiotics, in order to improve their effectiveness of and overcome antibiotic resistance.


Decreased systemic iron levels reduce erythropoiesis and are responsible for the so-called anemia of chronic disease (ACD). ACD is considered the second most prevalent anemia worldwide, after iron deficiency anemia, and is linked to a wide range of chronic infections and autoimmune diseases (Table 2). In recent literature it remains unclear whether ACD is marker of disease severity and progression or a causative factor (49). In patients suffering from ACD, the natural response of increasing erythropoietin with decreasing levels of hemoglobin is weakened and proliferation and differentiation of erythroid precursors is diminished. The resulting reduced hemoglobin levels can impact morbidity and mortality (50). ACD results from the bodies defense mechanism against invading bacteria, therefore the best treatment is curing the underlying inflammatory/infectious disease. In other clinical conditions, low plasma iron levels characteristic of anemia are treated with oral or intravenous iron supplementation. However, this treatment is of concern in critically ill patients as iron potentiates bacterial growth (51). Furthermore, studies found intravenous administration of iron to be associated with an increased risk of all cause infection (52).

Table 2 Disease groups in which anemia of chronic disease is common (49)
Disease Groups
Immune-mediated diseases
Inflammatory diseases
Chronic kidney diseases
Anemia of critical illness
Congestive heart failure
Anemia of the elderly
Chronic pulmonary disease

In conclusion, iron balance is necessary in order to treat acute infections. Iron is crucial during the host’s innate immune response (i.e. ROS production). However, iron restriction proves effective in reducing bacterial proliferation. Bacteria with enhanced iron uptake mechanisms (e.g., Klebsiella pneumoniae) have been shown to have increased virulence. Therefore, methods for targeting bacterial iron uptake present as a strategy to provide bacterial iron starvation without depriving the host. Synthetic iron chelators enhance the hosts innate iron withholding mechanisms and have been shown to reduce viability of bacteria. Recent studies demonstrate the ability of iron chelators, in combination with antibiotics, to not only improve the effectiveness of antibiotics but to overcome antibiotic resistance. Future studies could use this knowledge to create combination therapies, using synthetic iron chelators, to treat life-threatening infections.

PuigSRamos-AlonsoLRomeroAMMartínez-PastorMTThe elemental role of iron in DNA synthesis and repairMetallomics2017914831500DOI: 10.1039/c7mt00116a
NeilandsJB Siderophores: Structure and Function of Microbial Iron Transport CompoundsJ Biol Chem19952702672326726DOI: 10.1074/jbc.270.45.26723
PonkaPCellular iron metabolism. Kidney Int 55, S2–S11 (2003)DOI: 10.1046/j.1523-1755.1999.055suppl.69002.x
ChuaACGGrahamRMTrinderDOlynykJKThe regulation of cellular iron metabolismCrit Rev Clin Lab Sci200744413459DOI: 10.1080/10408360701428257
ChifmanJLaubenbacherRTortiS VA systems biology approach to iron metabolismAdv Exp Med Biol2014844201225DOI: 10.1007/978-1-4939-2095-2_10
GammellaEBurattiPCairoGRecalcatiSThe transferrin receptor: The cellular iron gateMetallomics201713671375DOI: 10.1039/c7mt00143f
AndrewsNCSchmidtPJIron Homeostasis.Annu Rev Physiol20066985DOI: 10.1146/annurev.physiol.69.031905.164337
AndrewsNCIron homeostasis: Insights from genetics and animal modelsNat Rev Genet20001208217DOI: 10.1038/35042073
NimehNBishopRCDisorders of iron metabolismMed Clin North Am198064631645DOI: 10.1016/S0025-7125(16)31585-1
RossiEHepcidin - the Iron Regulatory HormoneClin Biochem Rev2005264749DOI: 10.1093/jamia/ocw047
ZouDMSunWLRelationship between hepatitis C virus infection and iron overloadChin Med J (Engl)2017130866871DOI: 10.4103/0366-6999.202737
TorresMAJonesJDGDanglJLReactive oxygen species signaling in response to pathogensPlant Physiol20061413738DOI: 10.1104/pp.106.079467
KehrerJPThe Haber-Weiss reaction and mechanisms of toxicityToxicology20001494350DOI: 10.1016/S0300-483X(00)00231-6
WrightingDMAndrewsNCInterleukin-6 induces hepcidin expression through STAT3Blood200610832043209DOI: 10.1182/blood-2006-06-027631
ArmitageAEEddowesLAGileadiUColeSSpottiswoodeNSelvakumarTAHoLPTownsendARMDrakesmithHHepcidin regulation by innate immune and infectious stimuliBlood201111841294139DOI: 10.1182/blood-2011-04-351957
RuulASaarBAnaemia of chronic diseaseEesti Arst201594538546DOI: 10.1056/NEJMra041809
NairzMHaschkaDDemetzEWeissGIron at the interface of immunity and infectionFront Pharmacol20145110DOI: 10.3389/fphar.2014.00152
EllermannMArthurJCSiderophore-mediated iron acquisition and modulation of host-bacterial interactionsFree Radic Biol Med20171056878DOI: 10.1016/j.freeradbiomed.2016.10.489
SahaMSarkarSSarkarBSharmaBKBhattacharjeeSTribediPMicrobial siderophores and their potential applications: a reviewEnviron Sci Pollut Res20162339843999DOI: 10.1007/s11356-015-4294-0
HamiltonJLUl-haqMICreaghALHaynesCAKizhakkedathuJNIron Binding and Iron Removal Efficiency of Desferrioxamine Based Polymeric Iron Chelators: Influence of Molecular Size and Chelator DensityMacromol Biosci201717112DOI: 10.1002/mabi.201600244
YawalkarSJMilestones in the research and development of desferrioxamineNephrol Dial Transplant199384042DOI: 10.1093/ndt/8.supp1.40
CoddRRichardson-SanchezTTelferTJGotsbacherMPAdvances in the Chemical Biology of Desferrioxamine BACS Chem Biol2018131125DOI: 10.1021/acschembio.7b00851
ParquetM del CSavageKAAllanDSAngMTCChenWLoganSMHolbeinBE Antibiotic resistant Acinetobacter baumannii is susceptible to the novel iron-sequestering anti-infective DIBI in vitro and in experimental pneumonia in miceAntimicrob Agents Chemother2019137DOI: 10.1128/AAC.00855-19
EtoDWatanabeKSaekiHOinumaKIOtaniKINobukuniMShiratori-TakanoHTakanoHBeppuTUedaKDivergent effects of desferrioxamine on bacterial growth and characteristicsJ Antibiot (Tokyo)201366199203DOI: 10.1038/ja.2012.111
HatcherHCSinghRNTortiFMTortiS VSynthetic and natural iron chelators: Therapeutic potential and clinical useFuture Med Chem2009116431670DOI: 10.4155/fmc.09.121
VermylenCWhat is new in iron overload?Eur J Pediatr2008167377381DOI: 10.1007/s00431-007-0604-y
PoggialiECassinerioEZanaboniLCappelliniMDAn update on iron chelation therapyBlood Transfus201210411422DOI: 10.2450/2012.0008-12
ThorburnTAaliMKostekLLeTourneau-PaciCColpPZhouJHolbeinBHoskinDLehmannCAnti-inflammatory effects of a novel iron chelator, DIBI, in experimental sepsisClin Hemorheol Microcirc201767110DOI: 10.3233/CH-179205
Moreau-MarquisSO’TooleGAStantonBATobramycin and FDA-approved iron chelators eliminate Pseudomonas aeruginosa biofilms on cystic fibrosis cellsAm J Respir Cell Mol Biol200941305313DOI: 10.1165/rcmb.2008-0299OC
LuoGSpellbergBGebremariamTLeeHXiongYQFrenchSWBayerAIbrahimASCombination therapy with iron chelation and vancomycin in treating murine staphylococcemiaEur J Clin Microbiol Infect Dis201433845851DOI: 10.1007/s10096-013-2023-5
Runyen-JaneckyLJRole and regulation of heme iron acquisition in gram-negative pathogensFront Cell Infect Microbiol20133111DOI: 10.3389/fcimb.2013.00055
CazaMKronstadJWShared and distinct mechanisms of iron acquisition by bacterial and fungal pathogens of humansFront Cell Infect Microbiol20133123DOI: 10.3389/fcimb.2013.00080
BilitewskiUBlodgettJAVDuhme-KlairAKDallavalleSLaschatSRoutledgeASchobertRChemical and Biological Aspects of Nutritional Immunity—Perspectives for New Anti-Infectives that Target Iron Uptake SystemsAngew Chemie - Int Ed2017561436014382DOI: 10.1002/anie.201701586
Sully EK Malachowa N Elmore BO Alexander SM Femling JK Gray BM DeLeo FR Otto M Cheung AL Edwards BS Sklar LA Horswill AR Hall PR Gresham HD Selective Chemical Inhibition of agr Quorum Sensing in Staphylococcus aureus Promotes Host Defense with Minimal Impact on Resistance PLoS Pathog 2014 10 1 14 DOI: 10.1371/journal.ppat.1004174
WandersmanCDelepelairePHaemophore functions revisitedMol Microbiol201285618631DOI: 10.1111/j.1365-2958.2012.08136.x
ShiratakiCShojiOTeradaMOzakiSISugimotoHShiroYWatanabeYInhibition of heme uptake in pseudomonas aeruginosa by its hemophore (HasAp) bound to synthetic metal complexesAngew Chemie - Int Ed20145328622866DOI: 10.1002/anie.201307889
MuryoiNTiedemannMTPluymMCheungJHeinrichsDEStillmanMJDemonstration of the iron-regulated surface determinant (Isd) heme transfer pathway in Staphylococcus aureusJ Biol Chem20082832812528136DOI: 10.1074/jbc. M802171200
ParrowNLFlemingREMinnickMFSequestration and Scavenging of Iron in InfectionInfect Immun20138135033514DOI: 10.1128/iai.00602-13
FreestonePPWilliamsPHHaighRDMaggsAFNealCPLyteMGrowth stimulation of intestinal commensal Escherichia coli by catecholamines: A possible contributory factor in trauma-induced sepsisShock200218465470DOI: 10.1097/00024382-200211000-00014
FillatMFThe fur (ferric uptake regulator) superfamily: Diversity and versatility of key transcriptional regulatorsArch Biochem Biophys20145464152DOI: 10.1016/
HancockVDahlMKlemmPAbolition of biofilm formation in urinary tract escherichia coli and klebsiella isolates by metal interference through competition for furAppl Environ Microbiol20107638363841DOI: 10.1128/AEM.00241-10
DicksonKLiuSZhouJLangilleMHolbeinBELehmannCSelective sensitivity of the gut microbiome to iron chelators in polybacterial abdominal sepsisMed Hypotheses20181206871DOI: 10.1016/j.mehy.2018.08.018
HoltKEWertheimHZadoksRNBakerSWhitehouseCADanceDJenneyAConnorTRHsuLYSeverinJBrisseSCaoHWilkschJGorrieCSchultzMBEdwardsDJNguyenK VanNguyenTVDaoTTMensinkMMinhV LeNhuNTKSchultszCKuntamanKNewtonPNMooreCEStrugnellRAThomsonNRGenomic analysis of diversity, population structure, virulence, and antimicrobial resistance in Klebsiella pneumoniae , an urgent threat to public health Proc Natl Acad Sci2015112E3574E3581DOI: 10.1073/pnas.1501049112
MislinGLASchalkIJSiderophore-dependent iron uptake systems as gates for antibiotic Trojan horse strategies against Pseudomonas aeruginosaMetallomics20146408420DOI: 10.1039/c3mt00359k
KinzelOTappeRGerusIBudzikiewiczHThe Synthesis and Antibacterial Activity of two Pyoverdin-ampicillin Conjugates, Entering Pseudomonas aeruginosa via the Pyoverdin-mediated Iron Uptake PathwayJ Antibiot (Tokyo)201251499507DOI: 10.7164/antibiotics.51.499
VentolaCL The Antibiotic Resistance: part 1: causes and threats. P T 40, 227–83 (2015) Retrieved from
VentolaCLThe antibiotic resistance crisis: part 2: management strategies and new agentsP T20154034452
SavageKAParquetM del CarmenAllanDSDavidsonRJHolbeinBELillyEAFidelPL Iron restriction to clinical isolates of candida albicans by the novel chelator dibi inhibits growth and increases sensitivity to azoles in vitro and in vivo in a murine model of experimental vaginitisAntimicrob Agents Chemother201862111DOI: 10.1128/AAC.02576-17
WeissGGanzTGoodnoughLTAnemia of inflammationBlood20191334050DOI: 10.1182/blood-2018-06-856500
CullisJAnameia of Chronic DiseaseClin Med (Northfield Il)201313193196DOI: 10.7861/clinmedicine.13-2-193
DochertyABTurgeonAFWalshTSBest practice in critical care: anaemia in acute and critical illnessTransfus Med201828181189DOI: 10.1111/tme.12505
LittonEXiaoJHoKMSafety and efficacy of intravenous iron therapy in reducing requirement for allogeneic blood transfusion: Systematic review and meta-analysis of randomised clinical trialsBMJ2013347210DOI: 10.1136/bmj.f4822
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