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

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.

2006 ◽  
Vol 5 (10) ◽  
pp. 1596-1603 ◽  
Author(s):  
Martin Eisendle ◽  
Markus Schrettl ◽  
Claudia Kragl ◽  
Daniela Müller ◽  
Paul Illmer ◽  
...  

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.


2020 ◽  
Vol 86 (13) ◽  
Author(s):  
Yarui Cheng ◽  
Tianyuan Zhang ◽  
Li Wang ◽  
Wenli Chen

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.


2010 ◽  
Vol 88 (3) ◽  
pp. 331-340 ◽  
Author(s):  
Magda Descorbeth ◽  
Madhu B. Anand-Srivastava

We have recently shown that A10 vascular smooth muscle cells (VSMCs) exposed to high glucose exhibited enhanced expression of Gαq and PLCβ proteins. Since high glucose has been reported to increase the levels of vasoactive peptides and oxidative stress, the present study was undertaken to investigate the implication of angiotensin II (Ang II), endothelin (ET)-1, and oxidative stress in the high glucose-induced enhanced expression of Gαq/11 and PLCβ proteins and associated signaling in A10 VSMCs. The levels of Gαq, Gα11, PLCβ-1, and PLCβ-2 proteins, as determined by Western blotting, were significantly higher in A10 VSMCs exposed to high glucose than in control cells. The elevated levels were restored to control values by the antioxidant diphenyleneiodonium (DPI), as well as by the antagonist of Ang II AT1 receptor losartan and the antagonists of ETA and ETB receptors BQ123 and BQ788, respectively. In addition, ET-1-stimulated production of inositol trisphosphate (IP3), which was enhanced by high glucose, was also restored toward control levels by DPI. Furthermore, the enhanced production of superoxide anion (O2–), increased NADPH oxidase activity, and enhanced expression of p22phox and p47phox proteins induced by high glucose were restored to control levels by losartan, BQ123, and BQ788. These results suggest that through increased oxidative stress, high glucose-induced enhanced levels of endogenous Ang II and ET-1 may contribute to the increased levels of Gαq/11 and mediated signaling in A10 VSMCs.


Author(s):  
Abinaya Raghavan ◽  
Pooja Rao ◽  
Jiri Neuzil ◽  
Dean L. Pountney ◽  
Sangeeta Nath

AbstractTunnelling nanotubes (TNTs) are an emerging route of long-range intercellular communication that mediate cell-to-cell exchange of cargo and organelles and contribute to maintaining cellular homeostasis by balancing diverse cellular stresses. Besides their role in intercellular communication, TNTs are implicated in several ways in health and disease. Transfer of pathogenic molecules or structures via TNTs can promote the progression of neurodegenerative diseases, cancer malignancy, and the spread of viral infection. Additionally, TNTs contribute to acquiring resistance to cancer therapy, probably via their ability to rescue cells by ameliorating various pathological stresses, such as oxidative stress, reactive oxygen species (ROS), mitochondrial dysfunction, and apoptotic stress. Moreover, mesenchymal stem cells play a crucial role in the rejuvenation of targeted cells with mitochondrial heteroplasmy and oxidative stress by transferring healthy mitochondria through TNTs. Recent research has focussed on uncovering the key regulatory molecules involved in the biogenesis of TNTs. However further work will be required to provide detailed understanding of TNT regulation. In this review, we discuss possible associations with Rho GTPases linked to oxidative stress and apoptotic signals in biogenesis pathways of TNTs and summarize how intercellular trafficking of cargo and organelles, including mitochondria, via TNTs plays a crucial role in disease progression and also in rejuvenation/therapy.


2019 ◽  
Author(s):  
Andrea Sass ◽  
Tom Coenye

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.


Sign in / Sign up

Export Citation Format

Share Document