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Microbiological Research 2018Siderophores, the secondary metabolite of various microorganisms are ferric ion specific chelators secreted under iron stressed condition. These non-ribosomal peptides... (Review)
Review
Siderophores, the secondary metabolite of various microorganisms are ferric ion specific chelators secreted under iron stressed condition. These non-ribosomal peptides have been classified as catecholate, hydroxamate, carboxylate and mixed types. Recent studies focus on discovery of possible mammalian siderophores. The biosynthesis pathway including non-ribosomal dependent as well as non-ribosomal independent pathways are of great interest now a days. Many significant roles of siderophores such as virulence in pathogens, oxidative stress tolerance, classification of organisms etc. are being discovered. Studies on siderophore utilization in bioremediation and other heavy metal chelation have increased in past decade. The iron chelation ability of siderophores is being recently studied with regards to malignant cancerous cells. Not only this, it has been found that they possess antimicrobial properties which can be utilized against number of microbes. This review covers all recent aspects of siderophore and its applications.
Topics: Anti-Bacterial Agents; Aspergillus; Bacteria; Biodegradation, Environmental; Biological Transport; Chelating Agents; Iron; Neoplasms; Oxidative Stress; Plants; Secondary Metabolism; Siderophores; Virulence
PubMed: 29103733
DOI: 10.1016/j.micres.2017.10.012 -
The Journal of Biological Chemistry Apr 2012Bacteria use tight-binding, ferric-specific chelators called siderophores to acquire iron from the environment and from the host during infection; animals use proteins... (Review)
Review
Bacteria use tight-binding, ferric-specific chelators called siderophores to acquire iron from the environment and from the host during infection; animals use proteins such as transferrin and ferritin to transport and store iron. Recently, candidate compounds that could serve endogenously as mammalian siderophore equivalents have been identified and characterized through associations with siderocalin, the only mammalian siderophore-binding protein currently known. Siderocalin, an antibacterial protein, acts by sequestering iron away from infecting bacteria as siderophore complexes. Candidate endogenous siderophores include compounds that only effectively transport iron as ternary complexes with siderocalin, explaining pleiotropic activities in normal cellular processes and specific disease states.
Topics: Animals; Anti-Bacterial Agents; Apoptosis; Biological Transport; Carrier Proteins; Catechols; Chelating Agents; Humans; Hydrogen-Ion Concentration; Immunity, Innate; Iron; Kinetics; Lipocalin-2; Lipocalins; Models, Biological; Models, Chemical; Siderophores
PubMed: 22389496
DOI: 10.1074/jbc.R111.311829 -
Cells Nov 2022Understanding the intrinsic mechanisms of bacterial competition is a fundamental question. Iron is an essential trace nutrient that bacteria compete for. The most...
BACKGROUND
Understanding the intrinsic mechanisms of bacterial competition is a fundamental question. Iron is an essential trace nutrient that bacteria compete for. The most prevalent manner for iron scavenging is through the secretion of siderophores. Although tremendous efforts have focused on elucidating the molecular mechanisms of siderophores biosynthesis, export, uptake, and regulation of siderophores, the ecological aspects of siderophore-mediated competition are not well understood.
METHODS
We performed predation and bacterial competition assays to investigate the function of siderophore transport on myxobacterial predation.
RESULTS
Deletion of , which encodes an iron chelate uptake ABC transporter family permease subunit, led to a reduction in myxobacterial predation and intracellular iron, but iron deficiency was not the predominant reason for the decrease in the predation ability of the ∆ mutant. We further confirmed that obstruction of siderophore transport decreased myxobacterial predation by investigating the function of a non-ribosomal peptide synthetase for siderophore biosynthesis, a TonB-dependent receptor, and a siderophore binding protein in . Our results showed that the obstruction of siderophores transport decreased myxobacterial predation ability through the downregulation of lytic enzyme genes, especially outer membrane vesicle (OMV)-specific proteins.
CONCLUSIONS
This work provides insight into the mechanism of siderophore-mediated competition in myxobacteria.
Topics: Myxococcales; Bacterial Proteins; Siderophores; Iron; Membrane Proteins; Bacteria; ATP-Binding Cassette Transporters
PubMed: 36496980
DOI: 10.3390/cells11233718 -
Current Opinion in Microbiology Aug 2011The opportunistic fungal pathogen Aspergillus fumigatus adapts to iron limitation by upregulation of iron uptake mechanisms including siderophore biosynthesis and... (Review)
Review
The opportunistic fungal pathogen Aspergillus fumigatus adapts to iron limitation by upregulation of iron uptake mechanisms including siderophore biosynthesis and downregulation of iron-consuming pathways to spare iron. These metabolic changes depend mainly on the transcription factor HapX. Consistent with the crucial role of iron in pathophysiology, genetic inactivation of either HapX or the siderophore system attenuates virulence of A. fumigatus in a murine model of aspergillosis. The differences in iron handling between mammals and fungi might serve to improve therapy and diagnosis of fungal infections.
Topics: Animals; Aspergillosis; Aspergillus fumigatus; Gene Expression Regulation, Fungal; Homeostasis; Host-Pathogen Interactions; Humans; Iron; Molecular Structure; Oxidative Stress; Siderophores; Spores, Fungal; Transcription, Genetic; Transcriptional Activation; Virulence
PubMed: 21724450
DOI: 10.1016/j.mib.2011.06.002 -
Archives of Microbiology Apr 2021Late wilt disease, caused by Cephalosporium maydis in maize plant, is one of the main economical diseases in Egypt. Therefore, to cope with this problem, we investigated...
Late wilt disease, caused by Cephalosporium maydis in maize plant, is one of the main economical diseases in Egypt. Therefore, to cope with this problem, we investigated the potentiality of plant growth promoting rhizobacteria in controlling this disease. Six strains (Bacillus subtilis, B. circulance, B. coagulanse, B. licheniformis, Pseudomonas fluroscence and P. koreensis) were screened for siderophore production, and using dual plate culture method and greenhouse experiment, antagonistic activity against C. maydis was studied. Using two superior strains, single and dual inoculation treatments in maize were applied in field experiment during the 2018 and 2019 seasons. Results indicated that B. subtilis and P. koreensis strains had shown the most qualitative and quantitative assays for siderophore production and antagonistic activities. In greenhouse, the most effective treatments on the pre- and post-emergence damping off as well as growth promotion of maize were T3 treatment (inoculated with B. subtilis), and T8 treatment (inoculated with P. koreensis). In field experiment, T5 treatment (inoculated with a mixture of B. subtilis and P. koreensis) showed significant increases in catalase (CAT), peroxidase (POX) and polyphenol oxidase (PPO) activities, as well as total chlorophyll and carotenoids than control treatments during the two growing seasons. In the same way, the highest effect in reducing infection and increasing the thickness of the sclerenchymatous sheath layer surrounding the vascular bundles in maize stem was observed and these results were a reflection of the increase in yield and yield parameters.
Topics: Ascomycota; Bacillus subtilis; Pseudomonas; Siderophores; Zea mays
PubMed: 33231747
DOI: 10.1007/s00203-020-02113-5 -
ACS Infectious Diseases Apr 2022Synthetic and naturally occurring siderophores and their conjugates provide access to the bacterial cytoplasm via active membrane transport. Previously, we displaced...
Synthetic and naturally occurring siderophores and their conjugates provide access to the bacterial cytoplasm via active membrane transport. Previously, we displaced iron with the radioactive isotope Ga to quantify and track in vitro and in vivo uptake and distribution of siderophore Trojan Horse antibiotic conjugates. Here, we introduce a multi-isotope tagging strategy to individually elucidate the fate of metal cargo and the ligand construct with radioisotopes Ga and I. We synthesized gallium(III) model complexes of a ciprofloxacin-functionalized linear desferrichrome (Ga-) and deferoxamine (Ga-) incorporating an iodo-tyrosine linker to enable radiolabeling using the metal-binding (Ga) and the cargo-conjugation site (I). Radiochemical experiments with , , and wt strains show that Ga-/ and Ga--I/-I have comparable uptake, indicating intact complex import and siderophore-mediated uptake. In naive mice, Ga-/ and Ga--I/-I demonstrate predominantly renal clearance; urine metabolite analysis indicates in vivo dissociation of Ga(III) is a likely mechanism of degradation for Ga-/ when compared to ligand radiolabeled compounds, Ga--I/-I, which remain >60% intact in urine. Cumulatively, this work demonstrates that a multi-isotope tagging strategy effectively elucidates the in vitro uptake, pharmacokinetics, and in vivo stability of xenometallomycins with modular chemical structures.
Topics: Animals; Ciprofloxacin; Escherichia coli; Ligands; Mice; Pseudomonas aeruginosa; Siderophores; Staphylococcus aureus
PubMed: 35319188
DOI: 10.1021/acsinfecdis.2c00005 -
Clinical Infectious Diseases : An... Nov 2019Iron is an essential nutrient for bacterial growth, replication, and metabolism. Humans store iron bound to various proteins such as hemoglobin, haptoglobin,...
Iron is an essential nutrient for bacterial growth, replication, and metabolism. Humans store iron bound to various proteins such as hemoglobin, haptoglobin, transferrin, ferritin, and lactoferrin, limiting the availability of free iron for pathogenic bacteria. However, bacteria have developed various mechanisms to sequester or scavenge iron from the host environment. Iron can be taken up by means of active transport systems that consist of bacterial small molecule siderophores, outer membrane siderophore receptors, the TonB-ExbBD energy-transducing proteins coupling the outer and the inner membranes, and inner membrane transporters. Some bacteria also express outer membrane receptors for iron-binding proteins of the host and extract iron directly from these for uptake. Ultimately, iron is acquired and transported into the bacterial cytoplasm. The siderophores are small molecules produced and released by nearly all bacterial species and are classified according to the chemical nature of their iron-chelating group (ie, catechol, hydroxamate, α-hydroxyl-carboxylate, or mixed types). Siderophore-conjugated antibiotics that exploit such iron-transport systems are under development for the treatment of infections caused by gram-negative bacteria. Despite demonstrating high in vitro potency against pathogenic multidrug-resistant bacteria, further development of several candidates had stopped due to apparent adaptive resistance during exposure, lack of consistent in vivo efficacy, or emergence of side effects in the host. However, cefiderocol, with an optimized structure, has advanced and has been investigated in phase 1 to 3 clinical trials. This article discusses the mechanisms implicated in iron uptake and the challenges associated with the design and utilization of siderophore-mimicking antibiotics.
Topics: Bacterial Infections; Cephalosporins; Drug Design; Drug Development; Drug Resistance, Bacterial; Gram-Negative Bacteria; Humans; Iron; Models, Molecular; Siderophores; beta-Lactams; Cefiderocol
PubMed: 31724044
DOI: 10.1093/cid/ciz825 -
Frontiers in Bioscience (Landmark... Jan 2009The production of iron-scavenging siderophores by the opportunistic animal pathogen Pseudomonas aeruginosa is a textbook example of public goods cooperation. This trait... (Review)
Review
The production of iron-scavenging siderophores by the opportunistic animal pathogen Pseudomonas aeruginosa is a textbook example of public goods cooperation. This trait provides an excellent model system with which to study cooperation. Further, the links between siderophore production and P. aeruginosa virulence allow us to investigate how pathogen ecology, social behaviour and pathology might be connected. We present here the results of basic research on the evolution and ecology of siderophore cooperation in this species. In particular, we explore the effects of population and community structure, iron regime and genomic mutation rate on the relative success of siderophore cooperators and cheats. We also present preliminary data on the links between siderophore production and another clinically-relevant social trait, biofilm formation. It is our hope that more realistic laboratory studies of siderophore cooperation in P. aeruginosa will eventually cast light on the roles played by social traits in long-term microbial infections.
Topics: Pseudomonas aeruginosa; Siderophores; Virulence
PubMed: 19273338
DOI: 10.2741/3516 -
Journal of Natural Products Mar 2022Bacteria use small molecules to impose strict regulation over the acquisition, uptake, and sequestration of transition metal ions. Low-abundance nutrient metals, such as...
Bacteria use small molecules to impose strict regulation over the acquisition, uptake, and sequestration of transition metal ions. Low-abundance nutrient metals, such as Fe(III), need to be scavenged from the environment by high-affinity chelating molecules called siderophores. Conversely, metal ions that become toxic at high concentrations need to be sequestered and detoxified. Often, bacteria produce a suite of compounds that bind various metal ions at different affinities in order to maintain homeostasis. Turnerbactin, a triscatecholate siderophore isolated from the intracellular shipworm symbiont T7901, is responsible for iron regulation and uptake. Herein, another series of compounds are described that complex with iron, copper, and molybdenum in solution. Teredinibactins belong to a class of metal-binding molecules that utilize a phenolate-thiazoline moiety in the coordination of metal ions. In contrast to other compounds in this class, such as yersiniabactin, the phenyl ring is decorated with a 2,4-dihydroxy-3-halo substitution pattern. UV-vis absorption spectroscopy based titration experiments with CuCl show the formation of an intermediate complex at substoichiometric concentrations and conversion to a copper-bound complex at 1:1 molar equiv.
Topics: Bacteria; Biological Transport; Ferric Compounds; Iron; Siderophores
PubMed: 35196451
DOI: 10.1021/acs.jnatprod.1c01049 -
Trends in Molecular Medicine Dec 2016Iron is an essential nutrient for life. During infection, a fierce battle of iron acquisition occurs between the host and bacterial pathogens. Bacteria acquire iron by... (Review)
Review
Iron is an essential nutrient for life. During infection, a fierce battle of iron acquisition occurs between the host and bacterial pathogens. Bacteria acquire iron by secreting siderophores, small ferric iron-binding molecules. In response, host immune cells secrete lipocalin 2 (also known as siderocalin), a siderophore-binding protein, to prevent bacterial reuptake of iron-loaded siderophores. To counter this threat, some bacteria can produce lipocalin 2-resistant siderophores. This review discusses the recently described molecular mechanisms of siderophore iron trafficking between host and bacteria, highlighting the therapeutic potential of exploiting pathogen siderophore machinery for the treatment of antibiotic-resistant bacterial infections. Because the latter reflect a persistent problem in hospital settings, siderophore-targeting or siderophore-based compounds represent a promising avenue to combat such infections.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Discovery; Host-Pathogen Interactions; Humans; Iron; Lipocalin-2; Siderophores
PubMed: 27825668
DOI: 10.1016/j.molmed.2016.10.005