scholarly journals The Intracellular Siderophore Ferricrocin Is Involved in Iron Storage, Oxidative-Stress Resistance, Germination, and Sexual Development in Aspergillus nidulans

2006 ◽  
Vol 5 (10) ◽  
pp. 1596-1603 ◽  
Author(s):  
Martin Eisendle ◽  
Markus Schrettl ◽  
Claudia Kragl ◽  
Daniela Müller ◽  
Paul Illmer ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Iron Uptake ◽  
Iron Starvation ◽  
Efficient Utilization ◽  
Intracellular Iron ◽  
Iron Storage ◽  
Peptide Synthetase ◽  
Increased Sensitivity ◽  
Intracellular Storage ◽  
And Oxidative Stress

ABSTRACT Iron is required by most organisms, but an excess of this metal is potentially toxic. Consequently, uptake and intracellular storage of iron are tightly controlled. The filamentous fungus A. nidulans lacks the iron storage compound ferritin but possesses an intracellular siderophore, which is accumulated in a highly regulated manner as iron-free desferri-ferricrocin or iron-containing ferricrocin via transcriptional regulation of the nonribosomal peptide synthetase SidC. Biosynthesis of desferri-ferricrocin was low during iron-replete conditions but up-regulated by both iron starvation and intracellular iron excess, the latter caused by either a shift from iron-depleted to high-iron conditions or deregulation of iron uptake. Consequently, ferricrocin constituted only about 5% of the total iron content under iron-replete conditions but up to 64% during conditions of intracellular excess. In contrast, during iron starvation, desferri-ferricrocin was accumulated, which appears to represent a proactive strategy to prevent iron toxicity. Accumulation of the intracellular siderophore was also up-regulated by oxidative stress, which underscores the intertwining of iron metabolism and oxidative stress. Lack of the intracellular siderophore causes pleiotropic effects, as SidC deficiency results in (i) less-efficient utilization of iron, indicated by reduced growth under iron-depleted conditions and a higher iron demand under iron-replete conditions, (ii) delayed germination under iron-depleted conditions, (iii) increased sensitivity of conidia to oxidative stress, and (iv) elimination of cleistothecia formation in homothallic conditions.

Dealing with oxidative stress and iron starvation in microorganisms: an overviewThis review is one of a selection of papers published in a Special Issue on Oxidative Stress in Health and Disease.

2010 ◽  
Vol 88 (3) ◽  
pp. 264-272 ◽  
Author(s):  
Julie-Anna M. Benjamin ◽  
Guillaume Desnoyers ◽  
Audrey Morissette ◽  
Hubert Salvail ◽  
Eric Massé
Keyword(s):  
Oxidative Stress ◽  
Cellular Response ◽  
Pathogenic Bacteria ◽  
Iron Starvation ◽  
Intracellular Iron ◽  
Iron Sulfur Clusters ◽  
Successful Infection ◽  
Health And Disease ◽  
And Oxidative Stress ◽  
Selection Of

Iron starvation and oxidative stress are 2 hurdles that bacteria must overcome to establish an infection. Pathogenic bacteria have developed many strategies to efficiently infect a broad range of hosts, including humans. The best characterized systems make use of regulatory proteins to sense the environment and adapt accordingly. For example, iron–sulfur clusters are critical for sensing the level and redox state of intracellular iron. The regulatory small RNA (sRNA) RyhB has recently been shown to play a central role in adaptation to iron starvation, while the sRNA OxyS coordinates cellular response to oxidative stress. These regulatory sRNAs are well conserved in many bacteria and have been shown to be essential for establishing a successful infection. An overview of the different strategies used by bacteria to cope with iron starvation and oxidative stress is presented here.

scholarly journals Transcriptome Analysis Reveals IsiA-Regulatory Mechanisms Underlying Iron Depletion and Oxidative-Stress Acclimation in Synechocystis sp. Strain PCC 6803

2020 ◽  
Vol 86 (13) ◽  
Author(s):  
Yarui Cheng ◽  
Tianyuan Zhang ◽  
Li Wang ◽  
Wenli Chen
Keyword(s):  
Oxidative Stress ◽  
Network Analysis ◽  
Iron Deficiency ◽  
Regulatory Mechanisms ◽  
Functional Modules ◽  
Iron Stress ◽  
Iron Starvation ◽  
Stress Acclimation ◽  
And Oxidative Stress ◽  
Coexpression Network Analysis

ABSTRACT Microorganisms in nature are commonly exposed to various stresses in parallel. The isiA gene encodes an iron stress-induced chlorophyll-binding protein which is significantly induced under iron starvation and oxidative stress. Acclimation of oxidative stress and iron deficiency was investigated using a regulatory mutant of the Synechocystis sp. strain PCC 6803. In this study, the ΔisiA mutant grew more slowly in oxidative-stress and iron depletion conditions compared to the wild-type (WT) counterpart under the same conditions. Thus, we performed transcriptome sequencing (RNA-seq) analysis of the WT strain and the ΔisiA mutant under double-stress conditions to obtain a comprehensive view of isiA-regulated genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed significant differences between the WT strain and ΔisiA mutant, mainly related to photosynthesis and the iron-sulfur cluster. The deletion of isiA affects the expression of various genes that are involved in cellular processes and structures, such as photosynthesis, phycobilisome, and the proton-transporting ATPase complex. Weighted gene coexpression network analysis (WGCNA) demonstrated three functional modules in which the turquoise module was negatively correlated with superoxide dismutase (SOD) activity. Coexpression network analysis identified several hub genes of each module. Cotranscriptional PCR and reads coverage using the Integrative Genomics Viewer demonstrated that isiA, isiB, isiC, ssl0461, and dfp belonged to the isi operon. Three sRNAs related to oxidative stress were identified. This study enriches our knowledge of IsiA-regulatory mechanisms under iron deficiency and oxidative stress. IMPORTANCE This study analyzed the impact of isiA deletion on the transcriptomic profile of Synechocystis. The isiA gene encodes an iron stress-induced chlorophyll-binding protein, which is significantly induced under iron starvation. The deletion of isiA affects the expression of various genes that are involved in photosynthesis and ABC transporters. WGCNA revealed three functional modules in which the blue module was correlated with oxidative stress. We further demonstrated that the isi operon contained the following five genes: isiA, isiB, isiC, ssl0461, and dfp by cotranscriptional PCR. Three sRNAs were identified that were related to oxidative stress. This study enhances our knowledge of IsiA-regulatory mechanisms under iron deficiency and oxidative stress.

scholarly journals Ferricrocin, a Siderophore Involved in Intra- and Transcellular Iron Distribution in Aspergillus fumigatus

2009 ◽  
Vol 75 (12) ◽  
pp. 4194-4196 ◽  
Author(s):  
Anja Wallner ◽  
Michael Blatzer ◽  
Markus Schrettl ◽  
Bettina Sarg ◽  
Herbert Lindner ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Iron Acquisition ◽  
Iron Starvation ◽  
Intracellular Iron ◽  
Iron Storage ◽  
Essential Metal ◽  
Iron Distribution ◽  
Iron Transporter

ABSTRACT Iron is an essential metal for virtually all organisms. Iron acquisition is well characterized for various organisms, whereas intracellular iron distribution is poorly understood. In contrast to bacteria, plants, and animals, most fungi lack ferritin-mediated iron storage but possess an intracellular siderophore shown to be involved in iron storage. Here we demonstrate that deficiency in the intracellular siderophore ferricrocin causes iron starvation in conidia of Aspergillus fumigatus, demonstrating that ferricrocin is also involved in intra- and transcellular iron distribution. Thus, ferricrocin represents the first intracellular iron transporter identified in any organism.

scholarly journals Antibacterial Action of Polyphosphate onPorphyromonas gingivalis

2010 ◽  
Vol 55 (2) ◽  
pp. 806-812 ◽  
Author(s):  
Ji-Hoi Moon ◽  
Jae-Hong Park ◽  
Jin-Yong Lee
Keyword(s):  
Oxidative Stress ◽  
Inoculum Size ◽  
Dilution Method ◽  
Agar Dilution Method ◽  
Iron Storage ◽  
Gram Negative ◽  
Dense Granules ◽  
Genes Encoding ◽  
Atypical Cells ◽  
And Oxidative Stress

ABSTRACTPolyphosphate [poly(P)] has antibacterial activity against various Gram-positive bacteria. In contrast, Gram-negative bacteria are generally resistant to poly(P). Here, we describe the antibacterial characterization of poly(P) against a Gram-negative periodontopathogen,Porphyromonas gingivalis. The MICs of pyrophosphate (Na4P2O7) and all poly(P) (Nan+ 2PnO3n+ 1;n= 3 to 75) tested for the bacterium by the agar dilution method were 0.24% and 0.06%, respectively. Orthophosphate (Na2HPO4) failed to inhibit bacterial growth. Poly-P75 was chosen for further study. In liquid medium, 0.03% poly-P75 was bactericidal againstP. gingivalisirrespective of the growth phase and inoculum size, ranging from 105to109cells/ml. UV-visible spectra of the pigments fromP. gingivalisgrown on blood agar with or without poly-P75 showed that poly-P75 reduced the formation of μ-oxo bisheme by the bacterium. Poly-P75 increased hemin accumulation on theP. gingivalissurface and decreased energy-driven uptake of hemin by the bacterium. The expression of the genes encoding hemagglutinins, gingipains, hemin uptake loci, chromosome replication, and energy production was downregulated, while that of the genes related to iron storage and oxidative stress was upregulated by poly-P75. The transmission electron microscope showed morphologically atypical cells with electron-dense granules and condensed nucleoid in the cytoplasm. Collectively, poly(P) is bactericidal againstP. gingivalis, in which hemin/heme utilization is disturbed and oxidative stress is increased by poly(P).

scholarly journals Low iron-induced small RNA BrrF regulates central metabolism and oxidative stress responses in Burkholderia cenocepacia

2019 ◽  
Author(s):  
Andrea Sass ◽  
Tom Coenye
Keyword(s):  
Oxidative Stress ◽  
Small Rna ◽  
Deletion Mutant ◽  
Wild Type Strain ◽  
Tca Cycle ◽  
Burkholderia Cenocepacia ◽  
Iron Starvation ◽  
Iron Depletion ◽  
In The Wild ◽  
And Oxidative Stress

AbstractBrrF is a Fur-regulated small RNA highly upregulated in Burkholderia cenocepacia under conditions of iron depletion. Its computationally predicted targets include iron-containing enzymes of the tricarboxylic acid (TCA) cycle such as aconitase and succinate dehydrogenase, as well as iron-containing enzymes responsible for the oxidative stress response, such as superoxide dismutase and catalase. Phenotypic and gene expression analysis of BrrF deletion and overexpression mutants show that the regulation of these genes is BrrF-dependent. Expression of acnA, fumA, sdhA and sdhC was downregulated during iron depletion in the wild type strain, but not in a BrrF deletion mutant. TCA cycle genes not predicted as target for BrrF were not affected in the same manner by iron depletion. Likewise, expression of sodB and katB was dowregulated during iron depletion in the wild type strain, but not in a BrrF deletion mutant. BrrF overexpression reduced aconitase and superoxide dismutase activities and increased sensitivity to hydrogen peroxide. All phenotypes and gene expression changes of the BrrF deletion mutant could be complemented by overexpressing BrrF in trans. Overall, BrrF acts as a regulator of central metabolism and oxidative stress response, possibly as an iron-sparing measure to maintain iron homeostasis under conditions of iron starvation.ImportanceRegulatory small RNAs play an essential role in maintaining cell homeostasis in bacteria in response to environmental stresses such as iron starvation. Prokaryotes generally encode a large number of RNA regulators, yet their identification and characterisation is still in its infancy for most bacterial species. Burkholderia cenocepacia is an opportunistic pathogen with high innate antimicrobial resistance, which can cause the often fatal cepacia syndrome in individuals with cystic fibrosis. In this study we characterise a small RNA which is involved in the response to iron starvation, a condition that pathogenic bacteria are likely to encounter in the host.

HFE Downregulates Iron Uptake From Transferrin and Induces Iron-Regulatory Protein Activity in Stably Transfected Cells

Blood ◽  
1999 ◽  
Vol 94 (11) ◽  
pp. 3915-3921 ◽  
Author(s):  
H.D. Riedel ◽  
M.U. Muckenthaler ◽  
S.G. Gehrke ◽  
I. Mohr ◽  
K. Brennan ◽  
...  
Keyword(s):  
Transferrin Receptor ◽  
Iron Uptake ◽  
Iron Homeostasis ◽  
Hereditary Hemochromatosis ◽  
Regulatory Protein ◽  
Intracellular Iron ◽  
Iron Storage ◽  
Iron Regulatory Proteins ◽  
Cellular Iron

Hereditary hemochromatosis (HH) is a common autosomal-recessive disorder of iron metabolism. More than 80% of HH patients are homozygous for a point mutation in a major histocompatibility complex (MHC) class I type protein (HFE), which results in a lack of HFE expression on the cell surface. A previously identified interaction of HFE and the transferrin receptor suggests a possible regulatory role of HFE in cellular iron absorption. Using an HeLa cell line stably transfected with HFE under the control of a tetracycline-sensitive promoter, we investigated the effect of HFE expression on cellular iron uptake. We demonstrate that the overproduction of HFE results in decreased iron uptake from diferric transferrin. Moreover, HFE expression activates the key regulators of intracellular iron homeostasis, the iron-regulatory proteins (IRPs), implying that HFE can affect the intracellular “labile iron pool.” The increase in IRP activity is accompanied by the downregulation of the iron-storage protein, ferritin, and an upregulation of transferrin receptor levels. These findings are discussed in the context of the pathophysiology of HH and a possible role of iron-responsive element (IRE)-containing mRNAs.

scholarly journals Random T-DNA Mutagenesis Identifies a Cu/Zn Superoxide Dismutase Gene as a Virulence Factor of Sclerotinia sclerotiorum

2013 ◽  
Vol 26 (4) ◽  
pp. 431-441 ◽  
Author(s):  
Liangsheng Xu ◽  
Weidong Chen
Keyword(s):  
Oxidative Stress ◽  
Growth Rate ◽  
Superoxide Dismutase ◽  
Sclerotinia Sclerotiorum ◽  
Virulence Factor ◽  
Wild Type ◽  
Expression Levels ◽  
Sclerotial Formation ◽  
Increased Sensitivity ◽  
And Oxidative Stress

Agrobacterium-mediated transformation (AMT) was used to identify potential virulence factors in Sclerotinia sclerotiorum. Screening AMT transformants identified two mutants showing significantly reduced virulence. The mutants showed growth rate, sclerotial formation, and oxalate production similar to that of the wild type. The mutation was due to a single T-DNA insertion at 212 bp downstream of the Cu/Zn superoxide dismutase (SOD) gene (SsSOD1, SS1G_00699). Expression levels of SsSOD1 were significantly increased under oxidative stresses or during plant infection in the wild-type strain but could not be detected in the mutant. SsSOD1 functionally complemented the Cu/Zn SOD gene in a Δsod1 Saccharomyces cerevisiae mutant. The SOD mutant had increased sensitivity to heavy metal toxicity and oxidative stress in culture and reduced ability to detoxify superoxide in infected leaves. The mutant also had reduced expression levels of other known pathogenicity genes such as endo-polygalacturanases sspg1 and sspg3. The functions of SsSOD1 were further confirmed by SsSOD1-deletion mutation. Like the AMT insertion mutant, the SsSOD1-deletion mutant exhibited normal growth rate, sclerotial formation, oxalate production, increased sensitivity to metal and oxidative stress, and reduced virulence. These results suggest that SsSOD1, while not being required for saprophytic growth and completion of the life cycle, plays critical roles in detoxification of reactive oxygen species during host–pathogen interactions and is an important virulence factor of Sclerotinia sclerotiorum.

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