scholarly journals Involvement of Peptidylprolylcis/transIsomerases in Enterococcus faecalis Virulence

2012 ◽  
Vol 80 (5) ◽  
pp. 1728-1735 ◽  
Author(s):  
Fany Reffuveille ◽  
Nathalie Connil ◽  
Maurizio Sanguinetti ◽  
Brunella Posteraro ◽  
Sylvie Chevalier ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protein Folding ◽  
Stress Response ◽  
Family Member ◽  
Enterococcus Faecalis ◽  
The Other ◽  
Manganese Concentration ◽  
High Manganese ◽  
Content Type ◽  
Quinolone Antibiotics

ABSTRACTPeptidylprolylcis/transisomerases (PPIases) are enzymes involved in protein folding. Analysis of the genome sequence ofEnterococcus faecalisV583 allowed for identification of 3 PPIases carrying genes.ef2898encodes an intracellular PPIase which was not shown to be important for theE. faecalisstress response or virulence. The other two PPIases, the parvulin family rotamase EF0685 and the cyclophilin family member EF1534, are expected to be surface-exposed proteins. They were shown to be important for virulence and resistance to NaCl. A Δef0685Δef1534mutant was also more resistant to oxidative stress, was able to grow under a high manganese concentration, and showed altered resistance to ampicillin and quinolone antibiotics.

Antimicrobial and antioxidant activity of pulp extracts from three populations of Ziziphus lotus L.

2019 ◽  
Vol 49 (6) ◽  
pp. 1014-1028 ◽  
Author(s):  
Chaimae Rais ◽  
Asmae Driouch ◽  
Chaimae Slimani ◽  
Aymane Bessi ◽  
Mounyr Balouiri ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antioxidant Activity ◽  
Enterococcus Faecalis ◽  
Methanol Extract ◽  
The Other ◽  
Aqueous Extracts ◽  
Bacteriostatic Effect ◽  
Content Type ◽  
Ethanol Extracts ◽  
Antimicrobial And Antioxidant Activity

Purpose This paper aims to evaluate the antimicrobial and antioxidant activity of ethanol, methanol and aqueous extracts of the jujube fruit. Design/methodology/approach The fruit samples were harvested from Ziziphus lotus L. in three regions of Morocco: Aïn Chifae (Immouzer), Saiss (Fez) and Guercif. The fruit extracts were obtained by Soxhlet method using ethanol, methanol and water, and then a phytochemical screening was done for each extract. Total phenolic and total flavonoids contents were also determined. Afterward, the antimicrobial activity of the studied extracts was evaluated using the broth microdilution method. To estimate the total antioxidant effect of these extracts, the DPPH (2,2-diphenyl-1-picrylhydrazyl) scavenging and phosphomolybdate tests were performed. Findings Results showed that the highest content of polyphenols and flavonoids was found for ethanol and methanol extracts, while the lowest content was found in the aqueous extracts for all populations studied. Thus, results showed that the highest content of phenolic compounds was recorded in the population of Fez. Methanol extract of this population was the richest in polyphenols (30.36 mg/g) and in flavonoids (13.03 mg/g). The antimicrobial tests showed that Enterococcus faecalis and Pseudomonas aeruginosa were the most sensitive (6.25 mg/ml), compared to the other tested strains. Based on the minimal bactericidal concentrations/minimal fungicidal concentration or MFC/MIC ratio, it seems that ethanol extracts showed a bactericidal effect against Escherichia coli, Staphylococcus aureus and Bacillus subtillis, and a bacteriostatic effect against Enterococcus faecalis. On the other hand, the methanol extract showed bacteriostatic effect against Enterococcus faecalis and Pseudomonas aeruginosa. In addition, methanol extracts of Ziziphus lotus have significant antioxidant potent. Originality/value Methanol and ethanol extracts of Ziziphus lotus fruit have demonstrated strong antimicrobial effect. Moreover, the authors were able to show that the extract of Ziziphus lotus fruit has a very important antioxidant power.

scholarly journals Catalase Expression inAzospirillum brasilenseSp7 Is Regulated by a Network Consisting of OxyR and Two RpoH Paralogs and Including an RpoE1→RpoH5 Regulatory Cascade

2018 ◽  
Vol 84 (23) ◽  
Author(s):  
Ashutosh Kumar Rai ◽  
Sudhir Singh ◽  
Sushil Kumar Dwivedi ◽  
Amit Srivastava ◽  
Parul Pandey ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Sinorhizobium Meliloti ◽  
Deinococcus Radiodurans ◽  
Oxidative Stress Response ◽  
Sigma Factors ◽  
Transcriptional Analysis ◽  
Content Type ◽  
Regulatory Cascade ◽  
Transcription Regulators

ABSTRACTThe genome ofAzospirillum brasilenseencodes five RpoH sigma factors: two OxyR transcription regulators and three catalases. The aim of this study was to understand the role they play during oxidative stress and their regulatory interconnection. Out of the 5 paralogs of RpoH present inA. brasilense, inactivation of onlyrpoH1rendersA. brasilenseheat sensitive. While transcript levels ofrpoH1were elevated by heat stress, those ofrpoH3andrpoH5were upregulated by H2O2. Catalase activity was upregulated inA. brasilenseand itsrpoH::kmmutants in response to H2O2except in the case of therpoH5::kmmutant, suggesting a role for RpoH5 in regulating inducible catalase. Transcriptional analysis of thekatN,katAI, andkatAII genes revealed that the expression ofkatNandkatAII was severely compromised in therpoH3::kmandrpoH5::kmmutants, respectively. Regulation ofkatNandkatAII by RpoH3 and RpoH5, respectively, was further confirmed in anEscherichia colitwo-plasmid system. Regulation ofkatAII by OxyR2 was evident by a drastic reduction in growth, KatAII activity, andkatAII::lacZexpression in anoxyR2::kmmutant. This study reports the involvement of RpoH3 and RpoH5 sigma factors in regulating oxidative stress response in alphaproteobacteria. We also report the regulation of an inducible catalase by a cascade of alternative sigma factors and an OxyR. Out of the three catalases inA. brasilense, those corresponding tokatNandkatAII are regulated by RpoH3 and RpoH5, respectively. The expression ofkatAII is regulated by a cascade of RpoE1→RpoH5 and OxyR2.IMPORTANCEIn silicoanalysis of theA. brasilensegenome showed the presence of multiple paralogs of genes involved in oxidative stress response, which included 2 OxyR transcription regulators and 3 catalases. So far,Deinococcus radioduransandVibrio choleraeare known to harbor two paralogs of OxyR, andSinorhizobium melilotiharbors three catalases. We do not yet know how the expression of multiple catalases is regulated in any bacterium. Here we show the role of multiple RpoH sigma factors and OxyR in regulating the expression of multiple catalases inA. brasilenseSp7. Our work gives a glimpse of systems biology ofA. brasilenseused for responding to oxidative stress.

scholarly journals EfaR Is a Major Regulator of Enterococcus faecalis Manganese Transporters and Influences Processes Involved in Host Colonization and Infection

2013 ◽  
Vol 81 (3) ◽  
pp. 935-944 ◽  
Author(s):  
M. C. Abrantes ◽  
J. Kok ◽  
M. de F. Lopes
Keyword(s):  
Oxidative Stress ◽  
Metal Ions ◽  
Enterococcus Faecalis ◽  
Bacterial Endocarditis ◽  
Nosocomial Pathogen ◽  
Host Colonization ◽  
Content Type ◽  
Bacterial Pathogenicity

ABSTRACTMetal ions, in particular manganese, are important modulators of bacterial pathogenicity. However, little is known about the role of manganese-dependent proteins in the nosocomial pathogenEnterococcus faecalis, a major cause of bacterial endocarditis. The present study demonstrates that the DtxR/MntR family metalloregulator EfaR ofE. faecaliscontrols the expression of several of its regulon members in a manganese-dependent way. We also show thatefaRinactivation impairs the ability ofE. faecalisto form biofilms, to survive inside macrophages, and to tolerate oxidative stress. Our results reveal that EfaR is an important modulator ofE. faecalisvirulence and link manganese homeostasis to enterococcal pathogenicity.

scholarly journals Nonthermal Plasma Induces the Viable-but-Nonculturable State in Staphylococcus aureus via Metabolic Suppression and the Oxidative Stress Response

2019 ◽  
Vol 86 (5) ◽  
Author(s):  
Xinyu Liao ◽  
Donghong Liu ◽  
Tian Ding
Keyword(s):  
Oxidative Stress ◽  
Staphylococcus Aureus ◽  
Stress Response ◽  
Nonthermal Plasma ◽  
Energy Allocation ◽  
Oxidative Stress Response ◽  
Vbnc State ◽  
Viable But Nonculturable ◽  
Content Type ◽  
Energy Dependent

ABSTRACT As a novel nonthermal technology, nonthermal plasma (NTP) has attracted a lot of attention. However, it could induce microorganisms into a viable but nonculturable (VBNC) state, posing a potential risk to food safety and public health. In this study, the molecular mechanisms of VBNC Staphylococcus aureus induced by NTP were investigated. With the use of a propidium monoazide quantitative PCR (PMA-qPCR) technique combined with a plate count method, we confirmed that 8.1 to 24.3 kJ NTP induced S. aureus into a VBNC state at a level of 7.4 to 7.6 log10 CFU/ml. The transcriptomic analysis was conducted and revealed that most energy-dependent physiological activities (e.g., metabolism) were arrested in VBNC S. aureus, while the oxidative stress response-related genes (katA, dps, msrB, msrA, and trxA) were significantly upregulated. In addition, this study showed that the ATP depletion by carbonyl cyanide m-chlorophenyl hydrazone (CCCP) pretreatment could accelerate the formation of VBNC S. aureus. The NTP-generated oxidative stress triggers the staphylococcal oxidative stress response, which consumes part of cellular energy (e.g., ATP). The energy allocation is therefore changed, and the energy assigned for other energy-dependent physiological activities (cell growth and division, etc.) is reduced, subsequently forcing S. aureus into a VBNC state. Therefore, the alterations of energy allocation should be some of the major contributors to the induction of VBNC S. aureus with NTP exposure. This study provides valuable knowledge for controlling the formation of VBNC S. aureus during NTP treatment. IMPORTANCE In recent years, nonthermal plasma (NTP) technology has received a lot of attention as a promising alternative to thermal pasteurization in the food industry. However, little is known about the microbial stress response toward NTP, which could be a potential risk to food safety and impede the development of NTP. A viable but nonculturable (VBNC) state is one of the most common survival strategies employed by microorganisms against external stress. This study investigated the mechanisms of the formation of VBNC Staphylococcus aureus by NTP in a more comprehensive and systematic aspect than had been done before. Our work confirmed that the NTP-generated oxidative stress induced changes in energy allocation as a driving force for the formation of VBNC S. aureus. This study could provide better knowledge for controlling the occurrence of VBNC S. aureus induced by NTP, which could lead to more rational design and ensure the development of safe foods.

scholarly journals Dps and DpsL Mediate SurvivalIn VitroandIn Vivoduring the Prolonged Oxidative Stress Response in Bacteroides fragilis

2015 ◽  
Vol 197 (20) ◽  
pp. 3329-3338 ◽  
Author(s):  
Michael I. Betteken ◽  
Edson R. Rocha ◽  
C. Jeffrey Smith
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Peritoneal Cavity ◽  
Bacteroides Fragilis ◽  
Oxidative Stress Response ◽  
Iron Storage ◽  
Content Type ◽  
Iron Storage Proteins

ABSTRACTBacteroides fragilisis a Gram-negative anaerobe and member of the human intestinal tract microbiome, where it plays many beneficial roles. However, translocation of the organism to the peritoneal cavity can lead to peritonitis, intra-abdominal abscess formation, bacteremia, and sepsis. During translocation,B. fragilisis exposed to increased oxidative stress from the oxygenated tissues of the peritoneal cavity and the immune response. In order to survive,B. fragilismounts a robust oxidative stress response consisting of an acute and a prolonged oxidative stress (POST) response. This report demonstrates that the ability to induce high levels of resistance totert-butyl hydroperoxide (tBOOH) after extended exposure to air can be linked to the POST response. Disk diffusion assays comparing the wild type to a Δdpsmutant and a ΔdpsΔbfrmutant showed greater sensitivity of the mutants to tBOOH after exposure to air, suggesting that Dps and DpsL play a role in the resistance phenotype. Complementation studies withdpsorbfr(encoding DpsL) restored tBOOH resistance, suggesting a role for both of these ferritin-family proteins in the response. Additionally, cultures treated with the iron chelator dipyridyl were not killed by tBOOH, indicating Dps and DpsL function by sequestering iron to prevent cellular damage. Anin vivoanimal model showed that the ΔdpsΔbfrmutant was attenuated, indicating that management of iron is important for survival within the abscess. Together, these data demonstrate a role for Dps and DpsL in the POST response which mediates survivalin vitroandin vivo.IMPORTANCEB. fragilisis the anaerobe most frequently isolated from extraintestinal opportunistic infections, but there is a paucity of information about the factors that allow this organism to survive outside its normal intestinal environment. This report demonstrates that the iron storage proteins Dps and DpsL protect against oxidative stress and that they contribute to survival bothin vitroandin vivo. Additionally, this work demonstrates an important role for the POST response inB. fragilissurvival and provides insight into the complex regulation of this response.

scholarly journals Necessity of OxyR for the Hydrogen Peroxide Stress Response and Full Virulence in Ralstonia solanacearum

2011 ◽  
Vol 77 (18) ◽  
pp. 6426-6432 ◽  
Author(s):  
Zomary Flores-Cruz ◽  
Caitilyn Allen
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Hydrogen Peroxide ◽  
Stress Response ◽  
Mutant Strain ◽  
Ralstonia Solanacearum ◽  
Oxidative Stress Response ◽  
Ros Scavenging ◽  
Content Type ◽  
Peroxide Stress

ABSTRACTThe plant pathogenRalstonia solanacearum, which causes bacterial wilt disease, is exposed to reactive oxygen species (ROS) during tomato infection and expresses diverse oxidative stress response (OSR) genes during midstage disease on tomato. TheR. solanacearumgenome predicts that the bacterium produces multiple and redundant ROS-scavenging enzymes but only one known oxidative stress response regulator, OxyR. AnR. solanacearumoxyRmutant had no detectable catalase activity, did not grow in the presence of 250 μM hydrogen peroxide, and grew poorly in the oxidative environment of solid rich media. This phenotype was rescued by the addition of exogenous catalase, suggesting thatoxyRis essential for the hydrogen peroxide stress response. Unexpectedly, theoxyRmutant strain grew better than the wild type in the presence of the superoxide generator paraquat. Gene expression studies indicated thatkatE,kaG,ahpC1,grxC, andoxyRitself were each differentially expressed in theoxyRmutant background and in response to hydrogen peroxide, suggesting thatoxyRis necessary for hydrogen peroxide-inducible gene expression. Additional OSR genes were differentially regulated in response to hydrogen peroxide alone. The virulence of theoxyRmutant strain was significantly reduced in both tomato and tobacco host plants, demonstrating thatR. solanacearumis exposed to inhibitory concentrations of ROSin plantaand that OxyR-mediated responses to ROS during plant pathogenesis are important forR. solanacearumhost adaptation and virulence.

scholarly journals A Point Mutation in the Transcriptional Repressor PerR Results in a Constitutive Oxidative Stress Response in Clostridioides difficile 630Δerm

mSphere ◽  
2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Daniel Troitzsch ◽  
Hao Zhang ◽  
Silvia Dittmann ◽  
Dorothee Düsterhöft ◽  
Timon Alexander Möller ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Reference Strain ◽  
Transcriptional Repressor ◽  
Oxidative Stress Response ◽  
Detailed Knowledge ◽  
Single Nucleotide ◽  
Content Type ◽  
Clostridioides Difficile ◽  
Model Strain

ABSTRACT The human pathogen Clostridioides difficile has evolved into the leading cause of nosocomial diarrhea. The bacterium is capable of spore formation, which even allows survival of antibiotic treatment. Although C. difficile features an anaerobic lifestyle, we determined a remarkably high oxygen tolerance of the laboratory reference strain 630Δerm. A mutation of a single nucleotide (single nucleotide polymorphism [SNP]) in the DNA sequence (A to G) of the gene encoding the regulatory protein PerR results in an amino acid substitution (Thr to Ala) in one of the helices of the helix-turn-helix DNA binding domain of this transcriptional repressor in C. difficile 630Δerm. PerR is a sensor protein for hydrogen peroxide and controls the expression of genes involved in the oxidative stress response. We show that PerR of C. difficile 630Δerm has lost its ability to bind the promoter region of PerR-controlled genes. This results in a constitutive derepression of genes encoding oxidative stress proteins such as a rubrerythrin (rbr1) whose mRNA abundance under anaerobic conditions was increased by a factor of about 7 compared to its parental strain C. difficile 630. Rubrerythrin repression in strain 630Δerm could be restored by the introduction of PerR from strain 630. The permanent oxidative stress response of C. difficile 630Δerm observed here should be considered in physiological and pathophysiological investigations based on this widely used model strain. IMPORTANCE The intestinal pathogen Clostridioides difficile is one of the major challenges in medical facilities nowadays. In order to better combat the bacterium, detailed knowledge of its physiology is mandatory. C. difficile strain 630Δerm was generated in a laboratory from the patient-isolated strain C. difficile 630 and represents a reference strain for many researchers in the field, serving as the basis for the construction of insertional gene knockout mutants. In our work, we demonstrate that this strain is characterized by an uncontrolled oxidative stress response as a result of a single-base-pair substitution in the sequence of a transcriptional regulator. C. difficile researchers working with model strain 630Δerm should be aware of this permanent stress response.

scholarly journals Transcriptional Landscape and Regulatory Roles of Small Noncoding RNAs in the Oxidative Stress Response of the HaloarchaeonHaloferax volcanii

2018 ◽  
Vol 200 (9) ◽  
Author(s):  
Diego Rivera Gelsinger ◽  
Jocelyne DiRuggiero
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Environmental Conditions ◽  
Noncoding Rnas ◽  
Oxidative Stress Response ◽  
Haloferax Volcanii ◽  
Peptidase Activity ◽  
Content Type ◽  
Functional Roles ◽  
Transcriptional Landscape

ABSTRACTHaloarchaea in their natural environment are exposed to hypersalinity, intense solar radiation, and desiccation, all of which generate high levels of oxidative stress. Previous work has shown that haloarchaea are an order of magnitude more resistant to oxidative stress than most mesophilic organisms. Despite this resistance, the pathways haloarchaea use to respond to oxidative stress damage are similar to those of nonresistant organisms, suggesting that regulatory processes might be key to their robustness. Recently, small regulatory noncoding RNAs (sRNAs) were discovered inArchaeaunder a variety of environmental conditions. We report here the transcriptional landscape and functional roles of sRNAs in the regulation of the oxidative stress response of the model haloarchaeonHaloferax volcanii. Thousands of sRNAs, both intergenic and antisense, were discovered using strand-specific sRNA sequencing (sRNA-seq), comprising 25 to 30% of the total transcriptome under no-challenge and oxidative stress conditions, respectively. We identified hundreds of differentially expressed sRNAs in response to hydrogen peroxide-induced oxidative stress inH. volcanii. The targets of a group of antisense sRNAs decreased in expression when these sRNAs were upregulated, suggesting that sRNAs are potentially playing a negative regulatory role on mRNA targets at the transcript level. Target enrichment of these antisense sRNAs included mRNAs involved in transposon mobility, chemotaxis signaling, peptidase activity, and transcription factors.IMPORTANCEWhile a substantial body of experimental work has been done to uncover the functions of small regulatory noncoding RNAs (sRNAs) in gene regulation inBacteriaandEukarya, the functional roles of sRNAs inArchaeaare still poorly understood. This study is the first to establish the regulatory effects of sRNAs on mRNAs during the oxidative stress response in the haloarchaeonHaloferax volcanii. Our work demonstrates that common principles for the response to a major cellular stress exist across the 3 domains of life while uncovering pathways that might be specific to theArchaea. This work also underscores the relevance of sRNAs in adaptation to extreme environmental conditions.

scholarly journals Loss of NADH Oxidase Activity in Streptococcus mutans Leads to Rex-Mediated Overcompensation in NAD+Regeneration by Lactate Dehydrogenase

2015 ◽  
Vol 197 (23) ◽  
pp. 3645-3657 ◽  
Author(s):  
J. L. Baker ◽  
A. M. Derr ◽  
R. C. Faustoferri ◽  
R. G. Quivey
Keyword(s):  
Oxidative Stress ◽  
Lactate Dehydrogenase ◽  
Stress Response ◽  
Streptococcus Mutans ◽  
Parent Strain ◽  
Nadh Oxidase ◽  
Oral Streptococci ◽  
Pathogenic Potential ◽  
Oral Pathogen ◽  
Content Type

ABSTRACTPrevious studies of the oral pathogenStreptococcus mutanshave determined that this Gram-positive facultative anaerobe mounts robust responses to both acid and oxidative stresses. The water-forming NADH oxidase (Nox; encoded bynox) is thought to be critical for the regeneration of NAD+, for use in glycolysis, and for the reduction of oxygen, thereby preventing the formation of damaging reactive oxygen species. In this study, the free NAD+/NADH ratio in anoxdeletion strain (Δnox) was discovered to be remarkably higher than that in the parent strain, UA159, when the strains were grown in continuous culture. This unanticipated result was explained by significantly elevated lactate dehydrogenase (Ldh; encoded byldh) activity andldhtranscription in the Δnoxstrain, which was mediated in part by the redox-sensing regulator Rex. cDNA microarray analysis ofS. mutanscultures exposed to simultaneous acid stress (growth at a low pH) and oxidative stress (generated through the deletion ofnoxor the addition of exogenous oxygen) revealed a stress response synergistically heightened over that with either stress alone. In the Δnoxstrain, this elevated stress response included increased glucose phosphoenolpyruvate phosphotransferase system (PTS) activity, which appeared to be due to elevatedmanLtranscription, mediated in part, like elevatedldhtranscription, by Rex. While the Δnoxstrain does possess a membrane composition different from that of the parent strain, it did not appear to have defects in either membrane permeability or ATPase activity. However, the altered transcriptome and metabolome of the Δnoxstrain were sufficient to impair its ability to compete with commensal peroxigenic oral streptococci during growth under aerobic conditions.IMPORTANCEStreptococcus mutansis an oral pathogen whose ability to outcompete commensal oral streptococci is strongly linked to the formation of dental caries. Previous work has demonstrated that theS. mutanswater-forming NADH oxidase is critical for both carbon metabolism and the prevention of oxidative stress. The results of this study show that upregulation of lactate dehydrogenase, mediated through the redox sensor Rex, overcompensates for the loss ofnox. Additionally,noxdeletion led to the upregulation of mannose and glucose transport, also mediated through Rex. Importantly, the loss ofnoxrenderedS. mutansdefective in its ability to compete directly with two species of commensal streptococci, suggesting a role fornoxin the pathogenic potential of this organism.

scholarly journals IdeR, a DtxR Family Iron Response Regulator, Controls Iron Homeostasis, Morphological Differentiation, Secondary Metabolism, and the Oxidative Stress Response inStreptomyces avermitilis

2018 ◽  
Vol 84 (22) ◽  
Author(s):  
Yaqing Cheng ◽  
Renjun Yang ◽  
Mengya Lyu ◽  
Shiwei Wang ◽  
Xingchao Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Secondary Metabolism ◽  
Iron Homeostasis ◽  
Morphological Differentiation ◽  
Oxidative Stress Response ◽  
Regulatory Role ◽  
Intracellular Iron ◽  
Content Type

ABSTRACTIron, an essential element for microorganisms, functions as a vital cofactor in a wide variety of key metabolic processes. On the other hand, excess iron may have toxic effects on bacteria by catalyzing the formation of reactive oxygen species through the Fenton reaction. The prevention of iron toxicity requires the precise control of intracellular iron levels in bacteria. Mechanisms of iron homeostasis in the genusStreptomyces(the producers of various antibiotics) are poorly understood.Streptomyces avermitilisis the industrial producer of avermectins, which are potent anthelmintic agents widely used in medicine, agriculture, and animal husbandry. We investigated the regulatory role of IdeR, a DtxR family regulator, inS. avermitilis. In the presence of iron, IdeR binds to a specific palindromic consensus sequence in promoters and regulates 14 targets involved in iron metabolism (e.g., iron acquisition, iron storage, heme metabolism, and Fe-S assembly). IdeR also directly regulates 12 targets involved in other biological processes, including morphological differentiation, secondary metabolism, carbohydrate metabolism, and the tricarboxylic acid (TCA) cycle.ideRtranscription is positively regulated by the peroxide-sensing transcriptional regulator OxyR. A newly constructedideRdeletion mutant (DideR) was found to be less responsive to iron levels and more sensitive to H2O2treatment than the wild-type strain, indicating thatideRis essential for oxidative stress responses. Our findings, taken together, demonstrate that IdeR plays a pleiotropic role in the overall coordination of metabolism inStreptomycesspp. in response to iron levels.IMPORTANCEIron is essential to almost all organisms, but in the presence of oxygen, iron is both poorly available and potentially toxic.Streptomycesspecies are predominantly present in soil where the environment is complex and fluctuating. So far, the mechanism of iron homeostasis inStreptomycesspp. remains to be elucidated. Here, we characterized the regulatory role of IdeR in the avermectin-producing organismS. avermitilis. IdeR maintains intracellular iron levels by regulating genes involved in iron absorption and storage. IdeR also directly regulates morphological differentiation, secondary metabolism, and central metabolism.ideRis under the positive control of OxyR and is indispensable for an efficient response to oxidative stress. This investigation uncovered that IdeR acts as a global regulator coordinating iron homeostasis, morphological differentiation, secondary metabolism, and oxidative stress response inStreptomycesspecies. Elucidation of the pleiotropic regulation function of IdeR provides new insights into the mechanisms of howStreptomycesspp. adapt to the complex environment.

Sign in / Sign up

Export Citation Format

Share Document