scholarly journals Iron Pathways and Iron Chelation Approaches in Viral, Microbial, and Fungal Infections

2020 ◽  
Vol 13 (10) ◽  
pp. 275
Author(s):  
Ravneet Chhabra ◽  
Aishwarya Saha ◽  
Ashkon Chamani ◽  
Nicole Schneider ◽  
Riya Shah ◽  
...  
Keyword(s):  
Iron Uptake ◽  
Fungal Infections ◽  
Iron Acquisition ◽  
Iron Chelation ◽  
Essential Element ◽  
Iron Availability ◽  
Tight Control ◽  
Potential Clinical Benefit ◽  
Bacteria And Fungi ◽  
Spread Of Infection

Iron is an essential element required to support the health of organisms. This element is critical for regulating the activities of cellular enzymes including those involved in cellular metabolism and DNA replication. Mechanisms that underlie the tight control of iron levels are crucial in mediating the interaction between microorganisms and their host and hence, the spread of infection. Microorganisms including viruses, bacteria, and fungi have differing iron acquisition/utilization mechanisms to support their ability to acquire/use iron (e.g., from free iron and heme). These pathways of iron uptake are associated with promoting their growth and virulence and consequently, their pathogenicity. Thus, controlling microorganismal survival by limiting iron availability may prove feasible through the use of agents targeting their iron uptake pathways and/or use of iron chelators as a means to hinder development of infections. This review will serve to assimilate findings regarding iron and the pathogenicity of specific microorganisms, and furthermore, find whether treating infections mediated by such organisms via iron chelation approaches may have potential clinical benefit.

scholarly journals StreptomycesVolatile Compounds Influence Exploration and Microbial Community Dynamics by Altering Iron Availability

mBio ◽  
2019 ◽  
Vol 10 (2) ◽  
Author(s):  
Stephanie E. Jones ◽  
Christine A. Pham ◽  
Matthew P. Zambri ◽  
Joseph McKillip ◽  
Erin E. Carlson ◽  
...  
Keyword(s):  
Microbial Community ◽  
Nutrient Availability ◽  
Iron Uptake ◽  
Community Dynamics ◽  
Critical Role ◽  
Iron Availability ◽  
Interspecies Interactions ◽  
Community Interactions ◽  
Content Type ◽  
Bacteria And Fungi

ABSTRACTBacteria and fungi produce a wide array of volatile organic compounds (VOCs), and these can act as chemical cues or as competitive tools. Recent work has shown that the VOC trimethylamine (TMA) can promote a new form ofStreptomycesgrowth, termed “exploration.” Here, we report that TMA also serves to alter nutrient availability in the area surrounding exploring cultures: TMA dramatically increases the environmental pH and, in doing so, reduces iron availability. This, in turn, compromises the growth of other soil bacteria and fungi. In response to this low-iron environment,Streptomyces venezuelaesecretes a suite of differentially modified siderophores and upregulates genes associated with siderophore uptake. Further reducing iron levels by limiting siderophore uptake or growing cultures in the presence of iron chelators enhanced exploration. Exploration was also increased whenS. venezuelaewas grown in association with the related low-iron- and TMA-tolerantAmycolatopsisbacteria, due to competition for available iron. We are only beginning to appreciate the role of VOCs in natural communities. This work reveals a new role for VOCs in modulating iron levels in the environment and implies a critical role for VOCs in modulating the behavior of microbes and the makeup of their communities. It further adds a new dimension to our understanding of the interspecies interactions that influenceStreptomycesexploration and highlights the importance of iron in exploration modulation.IMPORTANCEMicrobial growth and community interactions are influenced by a multitude of factors. A new mode ofStreptomycesgrowth—exploration—is promoted by interactions with the yeastSaccharomycescerevisiaeand requires the emission of trimethylamine (TMA), a pH-raising volatile compound. We show here that TMA emission also profoundly alters the environment around exploring cultures. It specifically reduces iron availability, and this in turn adversely affects the viability of surrounding microbes. Paradoxically,Streptomycesbacteria thrive in these iron-depleted niches, both rewiring their gene expression and metabolism to facilitate iron uptake and increasing their exploration rate. Growth in close proximity to other microbes adept at iron uptake also enhances exploration. Collectively, the data from this work reveal a new role for bacterial volatile compounds in modulating nutrient availability and microbial community behavior. The results further expand the repertoire of interspecies interactions and nutrient cues that impactStreptomycesexploration and provide new mechanistic insight into this unique mode of bacterial growth.

Molecular mechanisms of iron uptake in eukaryotes

1996 ◽  
Vol 76 (1) ◽  
pp. 31-47 ◽  
Author(s):  
D. M. de Silva ◽  
C. C. Askwith ◽  
J. Kaplan
Keyword(s):  
Iron Uptake ◽  
Mammalian Cells ◽  
Iron Homeostasis ◽  
Molecular Mechanisms ◽  
Iron Acquisition ◽  
Genetic Disorders ◽  
Essential Element ◽  
Recent Developments

Iron serves essential functions in both prokaryotes and eukaryotes, and cells have highly specialized mechanisms for acquiring and handling this metal. The primary mechanism by which the concentration of iron in biologic systems is controlled is through the regulation of iron uptake. Although the role of transferrin in mammalian iron homeostasis has been well characterized, the study of genetic disorders of iron metabolism has revealed other, transferrin-independent, mechanisms by which cells can acquire iron. In an attempt to understand how eukaryotic systems take up this essential element, investigators have begun studying the simple eukaryote Saccharomyces cerevisiae. Several genes have been identified and cloned that act in concert to allow iron acquisition from the environment. Some of these genes appear to have functional homologues in human systems. This review focuses on the recent developments in understanding eukaryotic iron uptake with an emphasis on the genetic and molecular characterization of these systems in both cultured mammalian cells and S. cerevisiae. An unexpected connection between iron and copper homeostasis has been revealed by recent genetic studies, which confirm biologic observations made several decades ago.

scholarly journals Conservation and Loss of a Putative Iron Utilization Gene Cluster among Genotypes of Aspergillus flavus

2021 ◽  
Vol 9 (1) ◽  
pp. 137
Author(s):  
Bishwo N. Adhikari ◽  
Kenneth A. Callicott ◽  
Peter J. Cotty
Keyword(s):  
Gene Cluster ◽  
Aspergillus Flavus ◽  
Iron Uptake ◽  
Ferric Iron ◽  
Iron Acquisition ◽  
Atmospheric Oxygen ◽  
Iron Availability ◽  
Specific Loss ◽  
Complete Deletion ◽  
Iron Utilization

Iron is an essential component for growth and development. Despite relative abundance in the environment, bioavailability of iron is limited due to oxidation by atmospheric oxygen into insoluble ferric iron. Filamentous fungi have developed diverse pathways to uptake and use iron. In the current study, a putative iron utilization gene cluster (IUC) in Aspergillus flavus was identified and characterized. Gene analyses indicate A. flavus may use reductive as well as siderophore-mediated iron uptake and utilization pathways. The ferroxidation and iron permeation process, in which iron transport depends on the coupling of these two activities, mediates the reductive pathway. The IUC identified in this work includes six genes and is located in a highly polymorphic region of the genome. Diversity among A. flavus genotypes is manifested in the structure of the IUC, which ranged from complete deletion to a region disabled by multiple indels. Molecular profiling of A. flavus populations suggests lineage-specific loss of IUC. The observed variation among A. flavus genotypes in iron utilization and the lineage-specific loss of the iron utilization genes in several A. flavus clonal lineages provide insight on evolution of iron acquisition and utilization within Aspergillus section Flavi. The potential divergence in capacity to acquire iron should be taken into account when selecting A. flavus active ingredients for biocontrol in niches where climate change may alter iron availability.

scholarly journals Iron acquisition system of Sphingobium sp. strain SYK-6, a degrader of lignin-derived aromatic compounds

2020 ◽  
Author(s):  
Masaya Fujita ◽  
Taichi Sakumoto ◽  
Kenta Tanatani ◽  
Hong Yang Yu ◽  
Kosuke Mori ◽  
...  
Keyword(s):  
Outer Membrane ◽  
Aromatic Compounds ◽  
Iron Uptake ◽  
Iron Acquisition ◽  
Essential Element ◽  
Acquisition System ◽  
Bacterial Degradation ◽  
Iron Acquisition System ◽  
Iron Transporter ◽  
Outer Membrane Transporters

AbstractIron, an essential element for all organisms, acts as a cofactor of enzymes in bacterial degradation of recalcitrant aromatic compounds. The bacterial family, Sphingomonadaceae comprises various degraders of recalcitrant aromatic compounds; however, little is known about their iron acquisition system. Here, we investigated the iron acquisition system in a model bacterium capable of degrading lignin-derived aromatics, Sphingobium sp. strain SYK-6. Analyses of SYK-6 mutants revealed that FiuA (SLG_34550), a TonB-dependent receptor (TBDR), was the major outer membrane iron transporter. Three other TBDRs encoded by SLG_04340, SLG_04380, and SLG_10860 also participated in iron uptake, and tonB2 (SLG_34550), one of the six tonB comprising the Ton complex which enables TBDR-mediated transport was critical for iron uptake. The ferrous iron transporter FeoB (SLG_36840) played an important role in iron uptake across the inner membrane. The promoter activities of most of the iron uptake genes were induced under iron-limited conditions, and their regulation is controlled by SLG_29410 encoding the ferric uptake regulator, Fur. Although feoB, among all the iron uptake genes identified is highly conserved in Sphingomonad strains, the outer membrane transporters seem to be diversified. Elucidation of the iron acquisition system promises better understanding of the bacterial degradation mechanisms of aromatic compounds.

scholarly journals The Adaptive Mechanism of Plants to Iron Deficiency via Iron Uptake, Transport, and Homeostasis

2019 ◽  
Vol 20 (10) ◽  
pp. 2424 ◽  
Author(s):  
Xinxin Zhang ◽  
Di Zhang ◽  
Wei Sun ◽  
Tianzuo Wang
Keyword(s):  
Iron Deficiency ◽  
Iron Uptake ◽  
Iron Homeostasis ◽  
Iron Acquisition ◽  
Essential Element ◽  
Transport Mechanisms ◽  
Iron Storage ◽  
Iron Deficient ◽  
Dicotyledonous Plants ◽  
Shed Light

Iron is an essential element for plant growth and development. While abundant in soil, the available Fe in soil is limited. In this regard, plants have evolved a series of mechanisms for efficient iron uptake, allowing plants to better adapt to iron deficient conditions. These mechanisms include iron acquisition from soil, iron transport from roots to shoots, and iron storage in cells. The mobilization of Fe in plants often occurs via chelating with phytosiderophores, citrate, nicotianamine, mugineic acid, or in the form of free iron ions. Recent work further elucidates that these genes’ response to iron deficiency are tightly controlled at transcriptional and posttranscriptional levels to maintain iron homeostasis. Moreover, increasing evidences shed light on certain factors that are identified to be interconnected and integrated to adjust iron deficiency. In this review, we highlight the molecular and physiological bases of iron acquisition from soil to plants and transport mechanisms for tolerating iron deficiency in dicotyledonous plants and rice.

scholarly journals Iron acquisition system of Sphingobium sp. strain SYK-6, a degrader of lignin-derived aromatic compounds

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Masaya Fujita ◽  
Taichi Sakumoto ◽  
Kenta Tanatani ◽  
HongYang Yu ◽  
Kosuke Mori ◽  
...  
Keyword(s):  
Outer Membrane ◽  
Aromatic Compounds ◽  
Iron Uptake ◽  
Iron Acquisition ◽  
Essential Element ◽  
Acquisition System ◽  
Bacterial Degradation ◽  
Iron Acquisition System ◽  
Iron Transporter ◽  
Outer Membrane Transporters

Abstract Iron, an essential element for all organisms, acts as a cofactor of enzymes in bacterial degradation of recalcitrant aromatic compounds. The bacterial family, Sphingomonadaceae comprises various degraders of recalcitrant aromatic compounds; however, little is known about their iron acquisition system. Here, we investigated the iron acquisition system in a model bacterium capable of degrading lignin-derived aromatics, Sphingobium sp. strain SYK-6. Analyses of SYK-6 mutants revealed that FiuA (SLG_34550), a TonB-dependent receptor (TBDR), was the major outer membrane iron transporter. Three other TBDRs encoded by SLG_04340, SLG_04380, and SLG_10860 also participated in iron uptake, and tonB2 (SLG_34540), one of the six tonB comprising the Ton complex which enables TBDR-mediated transport was critical for iron uptake. The ferrous iron transporter FeoB (SLG_36840) played an important role in iron uptake across the inner membrane. The promoter activities of most of the iron uptake genes were induced under iron-limited conditions, and their regulation is controlled by SLG_29410 encoding the ferric uptake regulator, Fur. Although feoB, among all the iron uptake genes identified is highly conserved in Sphingomonad strains, the outer membrane transporters seem to be diversified. Elucidation of the iron acquisition system promises better understanding of the bacterial degradation mechanisms of aromatic compounds.

scholarly journals Identification of an ABC Transporter Required for Iron Acquisition and Virulence in Mycobacterium tuberculosis

2006 ◽  
Vol 188 (2) ◽  
pp. 424-430 ◽  
Author(s):  
G. Marcela Rodriguez ◽  
Issar Smith
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Abc Transporter ◽  
Iron Uptake ◽  
Chromosomal Region ◽  
Iron Acquisition ◽  
Iron Availability ◽  
Human Macrophages ◽  
Iron Deficient ◽  
Mouse Lungs ◽  
Siderophore Synthesis

ABSTRACT Iron availability affects the course of tuberculosis infection, and the ability to acquire this metal is known to be essential for replication of Mycobacterium tuberculosis in human macrophages. M. tuberculosis overcomes iron deficiency by producing siderophores. The relevance of siderophore synthesis for iron acquisition by M. tuberculosis has been demonstrated, but the molecules involved in iron uptake are currently unknown. We have identified two genes (irtA and irtB) encoding an ABC transporter similar to the YbtPQ system involved in iron transport in Yersinia pestis. Inactivation of the irtAB system decreases the ability of M. tuberculosis to survive iron-deficient conditions. IrtA and -B do not participate in siderophore synthesis or secretion but are required for efficient utilization of iron from Fe-carboxymycobactin, as well as replication of M. tuberculosis in human macrophages and in mouse lungs. We postulate that IrtAB is a transporter of Fe-carboxymycobactin. The irtAB genes are located in a chromosomal region previously shown to contain genes regulated by iron and the major iron regulator IdeR. Taken together, our results and previous observations made by other groups regarding two other genes in this region indicate that this gene cluster is dedicated to siderophore synthesis and transport in M. tuberculosis.

scholarly journals Iron Chelation in Local Infection

Molecules ◽  
2021 ◽  
Vol 26 (1) ◽  
pp. 189
Author(s):  
Cassidy Scott ◽  
Gaurav Arora ◽  
Kayle Dickson ◽  
Christian Lehmann
Keyword(s):  
Review Paper ◽  
Iron Chelation ◽  
Essential Element ◽  
Innate Immune ◽  
Iron Regulation ◽  
Oxygen Species ◽  
Iron Availability ◽  
Local Infection ◽  
Physiological Regulation ◽  
Iron Deprivation

Iron is an essential element in multiple biochemical pathways in humans and pathogens. As part of the innate immune response in local infection, iron availability is restricted locally in order to reduce overproduction of reactive oxygen species by the host and to attenuate bacterial growth. This physiological regulation represents the rationale for the therapeutic use of iron chelators to support induced iron deprivation and to treat infections. In this review paper we discuss the importance of iron regulation through examples of local infection and the potential of iron chelation in treating infection.

scholarly journals Bacterial effector targeting of a plant iron sensor facilitates iron acquisition and pathogen colonization

2021 ◽  
Author(s):  
Yingying Xing ◽  
Ning Xu ◽  
Deepak D Bhandari ◽  
Dmitry Lapin ◽  
Xinhua Sun ◽  
...  
Keyword(s):  
Pseudomonas Syringae ◽  
Iron Uptake ◽  
Iron Acquisition ◽  
Iron Accumulation ◽  
Regulatory Proteins ◽  
Mineral Nutrient ◽  
Effector Protein ◽  
Iron Regulatory Proteins ◽  
Protein Levels ◽  
Pathogen Colonization

Abstract Acquisition of nutrients from different species is necessary for pathogen colonization. Iron is an essential mineral nutrient for nearly all organisms, but little is known about how pathogens manipulate plant hosts to acquire iron. Here, we report that AvrRps4, an effector protein delivered by Pseudomonas syringae bacteria to plants, interacts with and targets the plant iron sensor protein BRUTUS (BTS) to facilitate iron uptake and pathogen proliferation in Arabidopsis thaliana. Infection of rps4 and eds1 by P. syringae pv. tomato (Pst) DC3000 expressing AvrRps4 resulted in iron accumulation, especially in the plant apoplast. AvrRps4 alleviates BTS-mediated degradation of bHLH115 and ILR3(IAA-Leucine resistant 3), two iron regulatory proteins. In addition, BTS is important for accumulating immune proteins Enhanced Disease Susceptibility1 (EDS1) at both the transcriptional and protein levels upon Pst (avrRps4) infections. Our findings suggest that AvrRps4 targets BTS to facilitate iron accumulation and BTS contributes to RPS4/EDS1-mediated immune responses.

Iron influences the expression of colonization factor CS6 of enterotoxigenic Escherichia coli

Microbiology ◽  
2021 ◽  
Vol 167 (9) ◽  
Author(s):  
Debjyoti Bhakat ◽  
Indranil Mondal ◽  
Asish Kumar Mukhopadhyay ◽  
Nabendu Sekhar Chatterjee
Keyword(s):  
Escherichia Coli ◽  
Promoter Activity ◽  
Iron Concentration ◽  
Iron Chelation ◽  
Enterotoxigenic Escherichia Coli ◽  
Watery Diarrhoea ◽  
Rna Expression ◽  
Iron Availability ◽  
Iron Salt ◽  
Ht 29

Enterotoxigenic Escherichia coli (ETEC) is a major pathogen of acute watery diarrhoea. The pathogenicity of ETEC is linked to adherence to the small intestine by colonization factors (CFs) and secretion of heat-labile enterotoxin (LT) and/or heat-stable enterotoxin (ST). CS6 is one of the most common CFs in our region and worldwide. Iron availability functions as an environmental cue for enteropathogenic bacteria, signalling arrival within the human host. Therefore, iron could modify the expression of CS6 in the intestine. The objective of this study was to determine the effect of iron availability on CS6 expression in ETEC. This would help in understanding the importance of iron during ETEC pathogenesis. ETEC strain harbouring CS6 was cultured under increasing concentrations of iron salt to assess the effect on CS6 RNA expression by quantitative RT-PCR, protein expression by ELISA, promoter activity by β-galactosidase activity, and epithelial adhesion on HT-29 cells. RNA expression of CS6 was maximum in presence of 0.2 mM iron (II) salt. The expression increased by 50-fold, which also reduced under iron-chelation conditions and an increased iron concentration of 0.4 mM or more. The surface expression of CS6 also increased by 60-fold in presence of 0.2 mM iron. The upregulation of CS6 promoter activity by 25-fold under this experimental condition was in accordance with the induction of CS6 RNA and protein. This increased CS6 expression was independent of ETEC strains. Bacterial adhesion to HT-29 epithelial cells was also enhanced by five-fold in the presence of 0.2 mM iron salt. These findings suggest that CS6 expression is dependent on iron concentration. However, with further increases in iron concentration beyond 0.2 mM CS6 expression is decreased, suggesting that there might be a strong regulatory mechanism for CS6 expression under different iron concentrations.

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