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 Global Regulatory Impact of ClpP Protease of Staphylococcus aureus on Regulons Involved in Virulence, Oxidative Stress Response, Autolysis, and DNA Repair

2006 ◽  
Vol 188 (16) ◽  
pp. 5783-5796 ◽  
Author(s):  
Antje Michel ◽  
Franziska Agerer ◽  
Christof R. Hauck ◽  
Mathias Herrmann ◽  
Joachim Ullrich ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Staphylococcus Aureus ◽  
Dna Repair ◽  
Stress Response ◽  
Oxidative Stress Response ◽  
Transcriptional Analysis ◽  
Expression Of Genes ◽  
Wide Range ◽  
Genes Encoding ◽  
Regulatory Impact

ABSTRACT Staphylococcus aureus is an important pathogen, causing a wide range of infections including sepsis, wound infections, pneumonia, and catheter-related infections. In several pathogens ClpP proteases were identified by in vivo expression technologies to be important for virulence. Clp proteolytic complexes are responsible for adaptation to multiple stresses by degrading accumulated and misfolded proteins. In this report clpP, encoding the proteolytic subunit of the ATP-dependent Clp protease, was deleted, and gene expression of ΔclpP was determined by global transcriptional analysis using DNA-microarray technology. The transcriptional profile reveals a strong regulatory impact of ClpP on the expression of genes encoding proteins that are involved in the pathogenicity of S. aureus and adaptation of the pathogen to several stresses. Expression of the agr system and agr-dependent extracellular virulence factors was diminished. Moreover, the loss of clpP leads to a complete transcriptional derepression of genes of the CtsR- and HrcA-controlled heat shock regulon and a partial derepression of genes involved in oxidative stress response, metal homeostasis, and SOS DNA repair controlled by PerR, Fur, MntR, and LexA. The levels of transcription of genes encoding proteins involved in adaptation to anaerobic conditions potentially regulated by an Fnr-like regulator were decreased. Furthermore, the expression of genes whose products are involved in autolysis was deregulated, leading to enhanced autolysis in the mutant. Our results indicate a strong impact of ClpP proteolytic activity on virulence, stress response, and physiology in S. aureus.

scholarly journals The Novel ncRNA OsiR Positively Regulates Expression of katE2 and is Required for Oxidative Stress Tolerance in Deinococcus radiodurans

2020 ◽  
Vol 21 (9) ◽  
pp. 3200 ◽  
Author(s):  
Lihua Gao ◽  
Xiaonan Chen ◽  
Ye Tian ◽  
Yongliang Yan ◽  
Yuhua Zhan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Stress Tolerance ◽  
Catalase Activity ◽  
Target Genes ◽  
Deinococcus Radiodurans ◽  
Oxidative Stress Response ◽  
Sequencing Analysis ◽  
Translation Efficiency ◽  
Oxidative Stress Tolerance

Deinococcus radiodurans is a polyextremophilic bacterium well known for its extreme resistance to irradiation, oxidative stress, and other damaging conditions. Many small noncoding RNAs (ncRNAs) in D. radiodurans have been identified by deep sequencing analysis and computational predictions. However, the precise roles of ncRNAs and their target genes in the oxidative stress response have not been investigated. Here, we report the identification and characterization of a novel ncRNA named OsiR (for oxidative stress-induced ncRNA). Oxidative stress tolerance analysis showed that deleting osiR significantly decreased viability, total antioxidant capacity, and catalase activity in D. radiodurans under oxidative stress conditions. Comparative phenotypic and qRT-PCR analyses of an osiR mutant identify a role of OsiR in regulating the expression of the catalase gene katE2. Microscale thermophoresis and genetic complementation showed that a 21-nt sequence in the stem–loop structure of OsiR (204–244 nt) directly base pairs with its counterpart in the coding region of katE2 mRNA (843–866 nt) via a 19 nt region. In addition, deletion of katE2 caused a significant reduction of catalase activity and oxidative stress tolerance similar to that observed in an osiR mutant. Our results show that OsiR positively regulates oxidative stress tolerance in D. radiodurans by increasing the mRNA stability and translation efficiency of katE2. This work provides a new regulatory pathway mediated by ncRNA for the oxidative stress response that most likely contributes to the extreme tolerances of D. radiodurans.

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 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.

scholarly journals Endoribonuclease YbeY Is Essential for RNA Processing and Virulence in Pseudomonas aeruginosa

mBio ◽  
2020 ◽  
Vol 11 (3) ◽  
Author(s):  
Yushan Xia ◽  
Yuding Weng ◽  
Congjuan Xu ◽  
Dan Wang ◽  
Xiaolei Pan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pseudomonas Aeruginosa ◽  
Stress Response ◽  
Small Rnas ◽  
Posttranscriptional Regulation ◽  
Oxidative Stress Response ◽  
Bacterial Virulence ◽  
Rrna Processing ◽  
Content Type ◽  
Stress Response Genes

ABSTRACT Posttranscriptional regulation plays an essential role in the quick adaptation of pathogenic bacteria to host environments, and RNases play key roles in this process by modifying small RNAs and mRNAs. We find that the Pseudomonas aeruginosa endonuclease YbeY is required for rRNA processing and the bacterial virulence in a murine acute pneumonia model. Transcriptomic analyses reveal that knocking out the ybeY gene results in downregulation of oxidative stress response genes, including the catalase genes katA and katB. Consistently, the ybeY mutant is more susceptible to H2O2 and neutrophil-mediated killing. Overexpression of katA restores the bacterial tolerance to H2O2 and neutrophil killing as well as virulence. We further find that the downregulation of the oxidative stress response genes is due to defective expression of the stationary-phase sigma factor RpoS. We demonstrate an autoregulatory mechanism of RpoS and find that ybeY mutation increases the level of a small RNA, ReaL, which directly represses the translation of rpoS through the 5′ UTR of its mRNA and subsequently reduces the expression of the oxidative stress response genes. In vitro assays demonstrate direct degradation of ReaL by YbeY. Deletion of reaL or overexpression of rpoS in the ybeY mutant restores the bacterial tolerance to oxidative stress and the virulence. We also demonstrate that YbeZ binds to YbeY and is involved in the 16S rRNA processing and regulation of reaL and rpoS as well as the bacterial virulence. Overall, our results reveal pleiotropic roles of YbeY and the YbeY-mediated regulation of rpoS through ReaL. IMPORTANCE The increasing bacterial antibiotic resistance imposes a severe threat to human health. For the development of effective treatment and prevention strategies, it is critical to understand the mechanisms employed by bacteria to grow in the human body. Posttranscriptional regulation plays an important role in bacterial adaptation to environmental changes. RNases and small RNAs are key players in this regulation. In this study, we demonstrate critical roles of the RNase YbeY in the virulence of the pathogenic bacterium Pseudomonas aeruginosa. We further identify the small RNA ReaL as the direct target of YbeY and elucidate the YbeY-regulated pathway on the expression of bacterial virulence factors. Our results shed light on the complex regulatory network of P. aeruginosa and indicate that inference with the YbeY-mediated regulatory pathway might be a valid strategy for the development of a novel treatment strategy.

scholarly journals Physiological and Transcriptional Responses of Candida parapsilosis to Exogenous Tyrosol

2019 ◽  
Vol 85 (20) ◽  
Author(s):  
Ágnes Jakab ◽  
Zoltán Tóth ◽  
Fruzsina Nagy ◽  
Dániel Nemes ◽  
Ildikó Bácskay ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Stress Response ◽  
Ethanol Fermentation ◽  
Ribosome Biogenesis ◽  
Candida Parapsilosis ◽  
Efflux Pump ◽  
Oxidative Stress Response ◽  
Antifungal Effect ◽  
Content Type

ABSTRACT Tyrosol plays a key role in fungal morphogenesis and biofilm development. Also, it has a remarkable antifungal effect at supraphysiological concentrations. However, the background of the antifungal effect remains unknown, especially in the case of non-albicans Candida species such as Candida parapsilosis. We examined the effect of tyrosol on growth, adhesion, redox homeostasis, virulence, as well as fluconazole susceptibility. To gain further insights into the physiological consequences of tyrosol treatment, we also determined genome-wide gene expression changes using transcriptome sequencing (RNA-Seq). A concentration of 15 mM tyrosol caused significant growth inhibition within 2 h of the addition of tyrosol, while the adhesion of yeast cells was not affected. Tyrosol increased the production of reactive oxygen species remarkably, as revealed by a dichlorofluorescein test, and it was associated with elevated superoxide dismutase, glutathione peroxidase, and catalase activities. The interaction between fluconazole and tyrosol was antagonistic. Tyrosol exposure resulted in 261 and 181 differentially expressed genes with at least a 1.5-fold increase or decrease in expression, respectively, which were selected for further study. Genes involved in ribosome biogenesis showed downregulation, while genes related to the oxidative stress response and ethanol fermentation were upregulated. In addition, tyrosol treatment upregulated the expression of efflux pump genes, including MDR1 and CDR1, and downregulated the expression of the FAD2 and FAD3 virulence genes involved in desaturated fatty acid formation. Our data demonstrate that exogenous tyrosol significantly affects the physiology and gene expression of C. parapsilosis, which could contribute to the development of treatments targeting quorum sensing in the future. IMPORTANCE Candida-secreted quorum-sensing molecules (i.e., farnesol and tyrosol) are key regulators in fungal physiology, which induce phenotypic adaptations, including morphological changes, altered biofilm formation, and synchronized expression of virulence factors. Moreover, they have a remarkable antifungal activity at supraphysiological concentrations. Limited data are available concerning the tyrosol-induced molecular and physiological effects on non-albicans Candida species such as C. parapsilosis. In addition, the background of the previously observed antifungal effect caused by tyrosol remains unknown. This study reveals that tyrosol exposure enhanced the oxidative stress response and the expression of efflux pump genes, while it inhibited growth and ribosome biogenesis as well as several virulence-related genes. Metabolism was changed toward glycolysis and ethanol fermentation. Furthermore, the initial adherence was not influenced significantly in the presence of tyrosol. Our results provide several potential explanations for the previously observed antifungal effect.

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