scholarly journals Iron homeostasis in the absence of ferricrocin and its consequences in fungal development and insect virulence in Beauveria bassiana

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jiraporn Jirakkakul ◽  
Nuchnudda Wichienchote ◽  
Somsak Likhitrattanapisal ◽  
Supawadee Ingsriswang ◽  
Thippawan Yoocha ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Beauveria Bassiana ◽  
Iron Homeostasis ◽  
Tca Cycle ◽  
Ergosterol Biosynthesis ◽  
Mitochondrial Activity ◽  
Wild Type ◽  
Iron Depletion ◽  
Fungal Entomopathogen ◽  
Insect Mortality

AbstractThe putative ferricrocin synthetase gene ferS in the fungal entomopathogen Beauveria bassiana BCC 2660 was identified and characterized. The 14,445-bp ferS encodes a multimodular nonribosomal siderophore synthetase tightly clustered with Fusarium graminearum ferricrocin synthetase. Functional analysis of this gene was performed by disruption with the bar cassette. ΔferS mutants were verified by Southern and PCR analyses. HPLC and TLC analyses of crude extracts indicated that biosynthesis of ferricrocin was abolished in ΔferS. Insect bioassays surprisingly indicated that ΔferS killed the Spodoptera exigua larvae faster (LT50 59 h) than wild type (66 h). Growth and developmental assays of the mutant and wild type demonstrated that ΔferS had a significant increase in germination under iron depletion and radial growth and a decrease in conidiation. Mitotracker staining showed that the mitochondrial activity was enriched in ΔferS under both iron excess and iron depletion. Comparative transcriptomes between wild type and ΔferS indicated that the mutant was increased in the expression of eight cytochrome P450 genes and those in iron homeostasis, ferroptosis, oxidative stress response, ergosterol biosynthesis, and TCA cycle, compared to wild type. Our data suggested that ΔferS sensed the iron excess and the oxidative stress and, in turn, was up-regulated in the antioxidant-related genes and those in ergosterol biosynthesis and TCA cycle. These increased biological pathways help ΔferS grow and germinate faster than the wild type and caused higher insect mortality than the wild type in the early phase of infection.

scholarly journals The Regulator PerR Is Involved in Oxidative Stress Response and Iron Homeostasis and Is Necessary for Full Virulence of Streptococcus pyogenes

2002 ◽  
Vol 70 (9) ◽  
pp. 4968-4976 ◽  
Author(s):  
Susanna Ricci ◽  
Robert Janulczyk ◽  
Lars Björck
Keyword(s):  
Oxidative Stress ◽  
Streptococcus Pyogenes ◽  
Stress Responses ◽  
Metal Binding ◽  
Iron Homeostasis ◽  
Bacterial Species ◽  
Transcriptional Analysis ◽  
Wild Type ◽  
Allelic Replacement

ABSTRACT Ferric uptake regulator (Fur) and Fur-like proteins form an important family of transcriptional regulators in many bacterial species. In this work we have characterized a Fur-like protein, the peroxide regulator PerR, in an M1 serotype of Streptococcus pyogenes. To determine the role of PerR in S. pyogenes, we inactivated the gene by allelic replacement. PerR-deficient bacteria showed 48% reduction of 55Fe incorporation from the culture medium. Transcriptional analysis revealed that mtsA, encoding a metal-binding protein of an ABC transporter in S. pyogenes, was transcribed at lower levels than were wild-type cells. Although total iron accumulation was reduced, the growth of the mutant strain was not significantly hampered. The mutant showed hyperresistance to hydrogen peroxide, and this response was induced in wild-type cells by growth in aerobiosis, suggesting that PerR acts as an oxidative stress-responsive repressor. PerR may also participate in the response to superoxide stress, as the perR mutant was more sensitive to the superoxide anion and had a reduced transcription of sodA, which encodes the sole superoxide dismutase of S. pyogenes. Complementation of the mutation with a functional perR gene restored 55Fe incorporation, response to peroxide stress, and transcription of both mtsA and sodA to levels comparable to those of wild-type bacteria. Finally, the perR mutant was attenuated in virulence in a murine air sac model of infection (P < 0.05). These results demonstrate that PerR is involved in the regulation of iron homeostasis and oxidative stress responses and that it contributes to the virulence of S. pyogenes.

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.

Transferrin Receptor 1 Up-Regulation Plays a Role in Iron Accumulation in a Murine Model of Sideroblastic Anemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3585-3585
Author(s):  
Florent M. Martin ◽  
Timothy J. Gilmartin ◽  
Gabriela Bydlon ◽  
Megan L. Welsh ◽  
Jeffrey S. Friedman
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Stem Cells ◽  
Transferrin Receptor ◽  
Iron Homeostasis ◽  
Oxygen Species ◽  
Wild Type ◽  
Sideroblastic Anemia ◽  
Hematopoietic Stem ◽  
Transferrin Receptor 1

Abstract Manganese superoxide dismutase (SOD2) detoxifies superoxide anion radicals generated by mitochondrial respiration (Weisiger and Fridovich, J. Biol. Chem. 1973). While SOD2-deficiency is lethal, SOD2-deficient (SOD2−/−) hematopoietic stem cells can rescue lethally irradiated wild-type mice. SOD2−/− hematopoietic chimeras show a persistent hemolytic anemia similar to human sideroblastic anemia (Friedman et al. J. Exp. Med. 2001). SOD2−/− erythroid progenitor cells have increased mitochondrial mass, and reticulocytes show mitochondrial iron deposition. Mature RBC show abundant siderotic granules, evidence of a defect in iron incorporation into heme, and shortened lifespan. SOD2−/− progenitors and mature RBC show both enhanced reactive oxygen species production and protein oxidative damage (Friedman et al. Blood 2004; Martin et al. Submitted). To define early events in the pathogenesis of the SOD2-deficiency anemia and, in particular to identify genes involved in the response of erythroid progenitors to oxidative stress, we compared gene expression of sorted TER-119+ CD71+ erythroblasts from SOD2−/−versus wild-type hematopoietic stem cells recipients. Using cDNA microarrays and class comparison analysis, we identified 600 transcripts as significantly discriminant between genotypes. Analysis showed that eleven transcripts encoding different subunits of the mitochondrial oxidative phosphorylation, ATP synthase, and TCA cycle were down-regulated in SOD2−/− erythroblasts. Previous work showed similar results at the protein level in SOD2−/− RBC (Friedman et al. Blood 2004) and at the activity level in specific tissues of SOD2−/− neonates prior to death (Melov et al. PNAS 1999). One interpretation is that SOD2−/− erythroblasts show metabolic decline. Of interest, a single transcript involved in iron homeostasis, Trfr, was found to be expressed at twice the levels found in wild-type erythroblasts (p&lt;0.0007, parametric p value). Trfr encodes transferrin receptor 1; two-fold up-regulation of transferrin receptor 1 was also shown at the protein level by flow cytometry analysis of SOD2−/− erythroblasts (p&lt;0.0001, unpaired two-tailed t-test). Transferrin receptor 1 is the cellular gatekeeper for iron uptake whose genetic inactivation induces abnormal erythropoiesis and iron homeostasis (Levy et al. Nat. Genet. 1999). The stability of the Trfr transcript is highly regulated by iron regulatory proteins (IRPs), that are known to be controlled by numerous effectors including reactive oxygen species (Hentze et al. Cell 2004, for review). We focus our current work on investigating, in vitro and in vivo, the role that up-regulation of transferrin receptor 1, likely through oxidative stress-mediated IRPs activity regulation, plays in iron overload in our SOD2-deficiency model. Taken together, our findings raise the possibility that increased iron delivery may be sufficient to cause sideroblastic anemia or may contribute to a self-reinforcing cycle where oxidative stress favors increased iron, and increased iron results in enhanced oxidative damage.

scholarly journals Mitochondria InfluenceCDR1Efflux Pump Activity, Hog1-Mediated Oxidative Stress Pathway, Iron Homeostasis, and Ergosterol Levels in Candida albicans

2013 ◽  
Vol 57 (11) ◽  
pp. 5580-5599 ◽  
Author(s):  
Edwina Thomas ◽  
Elvira Roman ◽  
Steven Claypool ◽  
Nikhat Manzoor ◽  
Jesús Pla ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Candida Albicans ◽  
Cellular Response ◽  
Iron Homeostasis ◽  
Sufficient Conditions ◽  
Ergosterol Biosynthesis ◽  
Biosynthesis Pathway ◽  
Content Type ◽  
Iron Assimilation ◽  
Increased Susceptibility

ABSTRACTMitochondrial dysfunction inCandida albicansis known to be associated with drug susceptibility, cell wall integrity, phospholipid homeostasis, and virulence. In this study, we deletedCaFZO1, a key component required during biogenesis of functional mitochondria. Cells withFZO1deleted displayed fragmented mitochondria, mitochondrial genome loss, and reduced mitochondrial membrane potential and were rendered sensitive to azoles and peroxide. In order to understand the cellular response to dysfunctional mitochondria, genome-wide expression profiling offzo1Δ/Δ cells was performed. Our results show that the increased susceptibility to azoles was likely due to reduced efflux activity ofCDRefflux pumps, caused by the missorting of Cdr1p into the vacuole. In addition,fzo1Δ/Δ cells showed upregulation of genes involved in iron assimilation, in iron-sufficient conditions, characteristic of iron-starved cells. One of the consequent effects was downregulation of genes of the ergosterol biosynthesis pathway with a commensurate decrease in cellular ergosterol levels. We therefore connect deregulated iron metabolism to ergosterol biosynthesis pathway in response to dysfunctional mitochondria. Impaired activation of the Hog1 pathway in the mutant was the basis for increased susceptibility to peroxide and increase in reactive oxygen species, indicating the importance of functional mitochondria in controlling Hog1-mediated oxidative stress response. Mitochondrial phospholipid levels were also altered as indicated by an increase in phosphatidylserine and phosphatidylethanolamine and decrease in phosphatidylcholine infzo1Δ/Δ cells. Collectively, these findings reinforce the connection between functional mitochondria and azole tolerance, oxidant-mediated stress, and iron homeostasis inC. albicans.

scholarly journals Transcriptional Response of Leptospira interrogans to Iron Limitation and Characterization of a PerR Homolog

2010 ◽  
Vol 78 (11) ◽  
pp. 4850-4859 ◽  
Author(s):  
Miranda Lo ◽  
Gerald L. Murray ◽  
Chen Ai Khoo ◽  
David A. Haake ◽  
Richard L. Zuerner ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Iron Homeostasis ◽  
Storage Proteins ◽  
Iron Acquisition ◽  
Bacterial Species ◽  
Transcriptional Response ◽  
Oxidative Stress Response ◽  
Wild Type ◽  
In The Wild

ABSTRACT Leptospirosis is a globally significant zoonosis caused by Leptospira spp. Iron is essential for growth of most bacterial species. Since iron availability is low in the host, pathogens have evolved complex iron acquisition mechanisms to survive and establish infection. In many bacteria, expression of iron uptake and storage proteins is regulated by Fur. L. interrogans encodes four predicted Fur homologs; we have constructed a mutation in one of these, la1857. We conducted microarray analysis to identify iron-responsive genes and to study the effects of la1857 mutation on gene expression. Under iron-limiting conditions, 43 genes were upregulated and 49 genes were downregulated in the wild type. Genes encoding proteins with predicted involvement in inorganic ion transport and metabolism (including TonB-dependent proteins and outer membrane transport proteins) were overrepresented in the upregulated list, while 54% of differentially expressed genes had no known function. There were 16 upregulated genes of unknown function which are absent from the saprophyte L. biflexa and which therefore may encode virulence-associated factors. Expression of iron-responsive genes was not significantly affected by mutagenesis of la1857, indicating that LA1857 is not a global regulator of iron homeostasis. Upregulation of heme biosynthetic genes and a putative catalase in the mutant suggested that LA1857 is more similar to PerR, a regulator of the oxidative stress response. Indeed, the la1857 mutant was more resistant to peroxide stress than the wild type. Our results provide insights into the role of iron in leptospiral metabolism and regulation of the oxidative stress response, including genes likely to be important for virulence.

An Anti-Apoptotic Molecule, Anamorsin, Functions in Both Iron-Sulfur Protein Assembly and Cellular Iron Homeostasis

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2106-2106 ◽  
Author(s):  
Akira Tanimura ◽  
Yuri Kondo ◽  
Hirokazu Tanaka ◽  
Itaru Matsumura ◽  
Tomohiko Ishibashi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Lines ◽  
Iron Homeostasis ◽  
Binding Activity ◽  
Wild Type ◽  
S Protein ◽  
Aconitase Activity ◽  
Cellular Iron ◽  
Iron Sulfur ◽  
Retrovirus Vector

Abstract Abstract 2106 Introduction: Anamorsin (AM, also called CIAPIN-1) is an anti-apoptotic factor, which we originally isolated as a molecule that confers factor-independent survival of hematopoietic cells (J.Exp.Med. 199:581–592, 2004). AM has no structural homology to any known anti-apoptosis molecules such as Bcl-2 and IAP family members. AM-deficient (AM−/−) mice are embryonic lethal at late gestation. Its embryos are anemic and the size of embryos is very small. It is thought that AM plays a crucial role in hematopoiesis, however the precise biological mechanisms of AM remain unclear. Recently, it was reported that the yeast AM homolog, Dre2, was implicated in cytosolic iron-sulfur (Fe/S) cluster assembly (Zhang Y., et al. Mol.Cell.Biol. 28:5569-5582, 2008). The AM carries conserved cysteine motifs (CX2CXC and twin CX2C) at its C termini, which may form iron binding sites. In this study, we have focused on the possibility that AM may be involved in the cellular iron regulation. Methods and Results: At first, in order to analyze molecular and cellular events, we established cell lines from wild-type or AM-deficient embryonic fetal liver (14.5dpc) by using SV40 large T antigen. We isolated 5 wild-type cell lines (AM WTs) and 2 AM-deficient cell lines (AM KOs) respectively. Next, we compared the cell growth and apoptosis in both cell lines and found that the growth rate of AM KOs were slightly lower than that of AM WTs although these cell lines were immortalized. AM KOs showed more significant apoptosis induced by oxidative stress; the percents of Annexin V positive fraction were 12 ± 4 and 36 ± 6 in AM WTs and AM KOs respectively under the condition of 0.1mM H2O2 for 16hr. In addition to oxidative stress, AM KOs were more sensitive to UV irradiation. These differences were cancelled by transduction of AM-expression retrovirus vector in AM KOs. It was reported that Dre2 functions in cytosolic Fe/S protein biogenesis. We examined whether AM might be involved in the maturation of cytosolic Fe/S proteins. Iron regulatory protein 1 (IRP1) is a well-known cytosolic Fe/S protein with dual functions; in the presence of an [4Fe-4S] cluster it functions as a cytosolic aconitase, while IRP1 binds to mRNA stem-loop structures called iron responsive elements (IREs) and confer the mRNA stability when the [4Fe-4S] cluster is missing. In the iron-deficient cells, IRP1 binds to IREs located at the mRNA of iron transferrin receptor (TfR), ferritin and other iron metabolism transcripts, thereby enhancing iron uptake. In this way, it is thought that IRP1 plays important roles in iron homeostasis. We therefore compared the aconitase activity and IRE binding activities of IRP1 between AM WTs and AM KOs and found that AM deficiency resulted in the decrease of cytosolic aconitase activity (approximately 30% compared to AM WTs). In contrast to cytosolic aconitase activity, the mitochondrial aconitase activity showed little change regardless of AM deficiency. In order to analyze whether AM deficiency might increase IRE binding activity of IRP1, cytoplasmic extracts of AM WTs and AM KOs were compared by RNA precipitation assay. In AM KOs, the expression level of IRP1 decreased approximately one third compared to AM WTs. However, the binding activity of IRP1 to biotin-labeled IRE increased in the extract of AM KOs approximately three-fold in comparison to AM WTs. These differences was cancelled by transduction of AM-expression retrovirus vector to AM KOs. All these findings demonstrated the involvement of AM in the maturation of the cytosolic Fe/S protein, IRP1. Furthermore, we examined the expression of TfR, which is known to be modulated by IRP1-mediated posttranscriptional regulation. In the presence of iron chelator, desferrioxamine, the expression of TfR in AM WTs was markedly elevated. On the other hand, in AM KOs, the expression of TfR was hardly elevated. Thus, it was showed that AM deficiency impaired the iron homeostasis and conferred low sensitivity for iron concentration due to the decreased function of IRP1. Conclusion: Our current findings indicate that AM is essential for cytosolic Fe/S cluster biogenesis and iron homeostasis. Now the influence of the AM-mediated iron homeostasis on hematopoiesis is under investigation. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Functional characterization of Fur in iron metabolism, oxidative stress resistance and virulence of Riemerella anatipestifer

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Mi Huang ◽  
Mafeng Liu ◽  
Jiajun Liu ◽  
Dekang Zhu ◽  
Qianying Tang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Iron Uptake ◽  
Iron Homeostasis ◽  
Functional Characterization ◽  
Uptake System ◽  
Rich Medium ◽  
Wild Type ◽  
Mobility Shift ◽  
Riemerella Anatipestifer ◽  
Excess Iron

AbstractIron is essential for most bacteria to survive, but excessive iron leads to damage by the Fenton reaction. Therefore, the concentration of intracellular free iron must be strictly controlled in bacteria. Riemerella anatipestifer (R. anatipestifer), a Gram-negative bacterium, encodes the iron uptake system. However, the iron homeostasis mechanism remains largely unknown. In this study, it was shown that compared with the wild type R. anatipestifer CH-1, R. anatipestifer CH-1Δfur was more sensitive to streptonigrin, and this effect was alleviated when the bacteria were cultured in iron-depleted medium, suggesting that the fur mutant led to excess iron accumulation inside cells. Similarly, compared with R. anatipestifer CH-1∆recA, R. anatipestifer CH-1∆recAΔfur was more sensitive to H2O2-induced oxidative stress when the bacteria were grown in iron-rich medium rather than iron-depleted medium. Accordingly, it was shown that R. anatipestifer CH-1∆recAΔfur produced more intracellular ROS than R. anatipestifer CH-1∆recA in iron-rich medium. Electrophoretic mobility shift assays showed that R. anatipestifer CH-1 Fur suppressed the transcription of putative iron uptake genes through binding to their promoter regions. Finally, it was shown that compared with the wild type, R. anatipestifer CH-1Δfur was significantly attenuated in ducklings and that the colonization ability of R. anatipestifer CH-1Δfur in various tissues or organs was decreased. All these results suggested that Fur is important for iron homeostasis in R. anatipestifer and its pathogenic mechanism.

scholarly journals Transcriptomic and Physiological Responses to Oxidative Stress in a Chlamydomonas reinhardtii Glutathione Peroxidase Mutant

Genes ◽  
2020 ◽  
Vol 11 (4) ◽  
pp. 463 ◽  
Author(s):  
Xiaocui Ma ◽  
Baolong Zhang ◽  
Rongli Miao ◽  
Xuan Deng ◽  
You Duan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Glutathione Peroxidase ◽  
Chlamydomonas Reinhardtii ◽  
Iron Homeostasis ◽  
Expression Profiles ◽  
Redox Homeostasis ◽  
Tca Cycle ◽  
Photosynthetic Organisms ◽  
Iron Assimilation ◽  
Different Levels

Aerobic photosynthetic organisms such as algae produce reactive oxygen species (ROS) as by-products of metabolism. ROS damage biomolecules such as proteins and lipids in cells, but also act as signaling molecules. The mechanisms that maintain the metabolic balance in aerobic photosynthetic organisms and how the cells specifically respond to different levels of ROS are unclear. Glutathione peroxidase (GPX) enzymes detoxify hydrogen peroxide or organic hydroperoxides, and thus are important components of the antioxidant system. In this study, we employed a Chlamydomonas reinhardtii glutathione peroxidase knockout (gpx5) mutant to identify the genetic response to singlet oxygen (1O2) generated by the photosensitizer rose bengal (RB). To this end, we compared the transcriptomes of the parental strain CC4348 and the gpx5 mutant sampled before, and 1 h after, the addition of RB. Functional annotation of differentially expressed genes showed that genes encoding proteins related to ROS detoxification, stress-response-related molecular chaperones, and ubiquitin–proteasome pathway genes were upregulated in CC4338. When GPX5 was mutated, higher oxidative stress specifically induced the TCA cycle and enhanced mitochondrial electron transport. Transcription of selenoproteins and flagellar-associated proteins was depressed in CC4348 and the gpx5 mutant. In addition, we found iron homeostasis played an important role in maintaining redox homeostasis, and we uncovered the relationship between 1O2 stress and iron assimilation, as well as selenoproteins. Based on the observed expression profiles in response to different levels of oxidative stress, we propose a model for dose-dependent responses to different ROS levels in Chlamydomonas.

scholarly journals The Small RNA RyhB Contributes to Siderophore Production and Virulence of Uropathogenic Escherichia coli

2014 ◽  
Vol 82 (12) ◽  
pp. 5056-5068 ◽  
Author(s):  
Gaëlle Porcheron ◽  
Rima Habib ◽  
Sébastien Houle ◽  
Mélissa Caza ◽  
François Lépine ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Escherichia Coli ◽  
Urinary Tract ◽  
Type Strain ◽  
Iron Homeostasis ◽  
Wild Type Strain ◽  
Iron Acquisition ◽  
Wild Type ◽  
Content Type ◽  
E Coli

ABSTRACTInEscherichia coli, the small regulatory noncoding RNA (sRNA) RyhB and the global ferric uptake regulator (Fur) mediate iron acquisition and storage control. Iron is both essential and potentially toxic for most living organisms, making the precise maintenance of iron homeostasis necessary for survival. While the roles of these regulators in iron homeostasis have been well studied in a nonpathogenicE. colistrain, their impact on the production of virulence-associated factors is still unknown for a pathogenicE. colistrain. We thus investigated the roles of RyhB and Fur in iron homeostasis and virulence of the uropathogenicE. coli(UPEC) strain CFT073. In a murine model of urinary tract infection (UTI), deletion offuralone did not attenuate virulence, whereas a ΔryhBmutant and a ΔfurΔryhBdouble mutant showed significantly reduced bladder colonization. The Δfurmutant was more sensitive to oxidative stress and produced more of the siderophores enterobactin, salmochelins, and aerobactin than the wild-type strain. In contrast, while RyhB was not implicated in oxidative stress resistance, the ΔryhBmutant produced lower levels of siderophores. This decrease was correlated with the downregulation ofshiA(encoding a transporter of shikimate, a precursor of enterobactin and salmochelin biosynthesis) andiucD(involved in aerobactin biosynthesis) in this mutant grown in minimal medium or in human urine.iucDwas also downregulated in bladders infected with the ΔryhBmutant compared to those infected with the wild-type strain. Our results thus demonstrate that the sRNA RyhB is involved in production of iron acquisition systems and colonization of the urinary tract by pathogenicE. coli.

scholarly journals The Negative Effect of Protein Phosphatase Z1 Deletion on the Oxidative Stress Tolerance of Candida albicans Is Synergistic with Betamethasone Exposure

2021 ◽  
Vol 7 (7) ◽  
pp. 540
Author(s):  
Ágnes Jakab ◽  
Tamás Emri ◽  
Kinga Csillag ◽  
Anita Szabó ◽  
Fruzsina Nagy ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Candida Albicans ◽  
Protein Phosphatase ◽  
Combined Treatment ◽  
Specific Protein ◽  
Ergosterol Biosynthesis ◽  
Acid Oxidation ◽  
Menadione Sodium Bisulfite ◽  
Rnaseq Data ◽  
Negative Effect

The glucocorticoid betamethasone (BM) has potent anti-inflammatory and immunosuppressive effects; however, it increases the susceptibility of patients to superficial Candida infections. Previously we found that this disadvantageous side effect can be counteracted by menadione sodium bisulfite (MSB) induced oxidative stress treatment. The fungus specific protein phosphatase Z1 (CaPpz1) has a pivotal role in oxidative stress response of Candida albicans and was proposed as a potential antifungal drug target. The aim of this study was to investigate the combined effects of CaPPZ1 gene deletion and MSB treatment in BM pre-treated C. albicans cultures. We found that the combined treatment increased redox imbalance, enhanced the specific activities of antioxidant enzymes, and reduced the growth in cappz1 mutant (KO) strain. RNASeq data demonstrated that the presence of BM markedly elevated the number of differentially expressed genes in the MSB treated KO cultures. Accumulation of reactive oxygen species, increased iron content and fatty acid oxidation, as well as the inhibiting ergosterol biosynthesis and RNA metabolic processes explain, at least in part, the fungistatic effect caused by the combined stress exposure. We suggest that the synergism between MSB treatment and CaPpz1 inhibition could be considered in developing of a novel combinatorial antifungal strategy accompanying steroid therapy.

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