scholarly journals The Onset of Tacrolimus Biosynthesis in Streptomyces tsukubaensis Is Dependent on the Intracellular Redox Status

Antibiotics ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 703
Author(s):  
Sílvia D. S. Pires ◽  
Rute Oliveira ◽  
Pedro Moradas-Ferreira ◽  
Marta V. Mendes
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Metabolic Flux ◽  
Redox Status ◽  
Oxidative Stress Response ◽  
Molecular Response ◽  
Streptomyces Tsukubaensis ◽  
The Impact ◽  
Intracellular Redox Status ◽  
Intracellular Redox

The oxidative stress response is a key mechanism that microorganisms have to adapt to changeling environmental conditions. Adaptation is achieved by a fine-tuned molecular response that extends its influence to primary and secondary metabolism. In the past, the role of the intracellular redox status in the biosynthesis of tacrolimus in Streptomyces tsukubaensis has been briefly acknowledged. Here, we investigate the impact of the oxidative stress response on tacrolimus biosynthesis in S. tsukubaensis. Physiological characterization of S. tsukubaensis showed that the onset of tacrolimus biosynthesis coincided with the induction of catalase activity. In addition, tacrolimus displays antioxidant properties and thus a controlled redox environment would be beneficial for its biosynthesis. In addition, S. tsukubaensis ∆ahpC strain, a strain defective in the H2O2-scavenging enzyme AhpC, showed increased production of tacrolimus. Proteomic and transcriptomic studies revealed that the tacrolimus over-production phenotype was correlated with a metabolic rewiring leading to increased availability of tacrolimus biosynthetic precursors. Altogether, our results suggest that the carbon source, mainly used for cell growth, can trigger the production of tacrolimus by modulating the oxidative metabolism to favour a low oxidizing intracellular environment and redirecting the metabolic flux towards the increase availability of biosynthetic precursors.

Borrelia burgdorferi bb0728encodes a coenzyme A disulphide reductase whose function suggests a role in intracellular redox and the oxidative stress response

2005 ◽  
Vol 59 (2) ◽  
pp. 475-486 ◽  
Author(s):  
Julie A. Boylan ◽  
Charles S. Hummel ◽  
Stéphane Benoit ◽  
Jorge Garcia-Lara ◽  
Jennifer Treglown-Downey ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Borrelia Burgdorferi ◽  
Coenzyme A ◽  
Oxidative Stress Response ◽  
Intracellular Redox

scholarly journals Redox-Dependent Condensation Of the Mycobacterial Nucleoid By WhiB4

2017 ◽  
Author(s):  
Manbeena Chawla ◽  
Saurabh Mishra ◽  
Pankti Parikh ◽  
Mansi Mehta ◽  
Prashant Shukla ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Mycobacterium Tuberculosis ◽  
Stress Response ◽  
Redox Homeostasis ◽  
Oxidative Stress Response ◽  
Chromosomal Structure ◽  
Redox Sensor ◽  
Intracellular Redox

AbstractOxidative stress response in bacteria is generally mediated through coordination between the regulators of oxidant-remediation systems (e.g.OxyR, SoxR) and nucleoid condensation (e.g.Dps, Fis). However, these genetic factors are either absent or rendered nonfunctional in the human pathogenMycobacterium tuberculosis(Mtb). Therefore, howMtborganizes genome architecture and regulates gene expression to counterbalance oxidative imbalance during infection is not known. Here, we report that an intracellular redox-sensor, WhiB4, dynamically links genome condensation and oxidative stress response inMtb. Disruption of WhiB4 affects the expression of genes involved in maintaining redox homeostasis, central carbon metabolism (CCM), respiration, cell wall biogenesis, DNA repair and protein quality control under oxidative stress. Notably, disulfide-linked oligomerization of WhiB4 in response to oxidative stress activates the protein’s ability to condense DNAin vitroandin vivo. Further, overexpression of WhiB4 led to hypercondensation of nucleoids, redox imbalance and increased susceptibility to oxidative stress, whereas WhiB4 disruption reversed this effect. In accordance with the findingsin vitro, ChIP-Seq data demonstrated non-specific binding of WhiB4 to GC-rich regions of theMtbgenome. Lastly, data indicate that WhiB4 deletion affected the expression of only a fraction of genes preferentially bound by the protein, suggesting its indirect effect on gene expression. We propose that WhiB4 is a novel redox-dependent nucleoid condensing protein that structurally couplesMtb’sresponse to oxidative stress with genome organization and transcription.Significance StatementMycobacterium tuberculosis (Mtb)needs to adapt in response to oxidative stress encountered inside human phagocytes. In other bacteria, condensation state of nucleoids modulates gene expression to coordinate oxidative stress response. However, this relation remains elusive inMtb. We performed molecular dissection of a mechanism controlled by an intracellular redox sensor, WhiB4, in organizing both chromosomal structure and selective expression of adaptive traits to counter oxidative stress inMtb. Using high-resolution sequencing, transcriptomics, imaging, and redox biosensor, we describe how WhiB4 modulates nucleoid condensation, global gene expression, and redox-homeostasis. WhiB4 over-expression hypercondensed nucleoids and perturbed redox homeostasis whereas WhiB4 disruption had an opposite effect. Our study discovered an empirical role for WhiB4 in integrating redox signals with nucleoid condensation inMtb.

scholarly journals PgRsp Is a Novel Redox-Sensing Transcription Regulator Essential for Porphyromonas gingivalis Virulence

2019 ◽  
Vol 7 (12) ◽  
pp. 623
Author(s):  
Michał Śmiga ◽  
Teresa Olczak
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Porphyromonas Gingivalis ◽  
Alternative Pathway ◽  
Redox Status ◽  
Oxidative Stress Response ◽  
Gene Encoding ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Redox Sensing

Porphyromonas gingivalis is one of the etiological agents of chronic periodontitis. Both heme and oxidative stress impact expression of genes responsible for its survival and virulence. Previously we showed that P. gingivalis ferric uptake regulator homolog affects expression of a gene encoding a putative Crp/Fnr superfamily member, termed P. gingivalis redox-sensing protein (PgRsp). Although PgRsp binds heme and shows the highest similarity to proteins assigned to the CooA family, it could be a member of a novel, separate family of proteins with unknown function. Expression of the pgrsp gene is autoregulated and iron/heme dependent. Genes encoding proteins engaged in the oxidative stress response were upregulated in the pgrsp mutant (TO11) strain compared with the wild-type strain. The TO11 strain showed higher biomass production, biofilm formation, and coaggregation ability with Tannerella forsythia and Prevotella intermedia. We suggest that PgRsp may regulate production of virulence factors, proteases, Hmu heme acquisition system, and FimA protein. Moreover, we observed growth retardation of the TO11 strain under oxidative conditions and decreased survival ability of the mutant cells inside macrophages. We conclude that PgRsp protein may play a role in the oxidative stress response using heme as a ligand for sensing changes in redox status, thus regulating the alternative pathway of the oxidative stress response alongside OxyR.

Altered intracellular redox status in Gaucher disease fibroblasts and impairment of adaptive response against oxidative stress

2007 ◽  
Vol 212 (1) ◽  
pp. 223-235 ◽  
Author(s):  
Marta Deganuto ◽  
Maria Gabriela Pittis ◽  
Alex Pines ◽  
Silvia Dominissini ◽  
Mark R. Kelley ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Adaptive Response ◽  
Gaucher Disease ◽  
Redox Status ◽  
Intracellular Redox Status ◽  
Intracellular Redox

scholarly journals A randomized observational analysis examining the correlation between patients’ food sensitivities, micronutrient deficiencies, oxidative stress response and immune redox status

2020 ◽  
Vol 10 (3) ◽  
pp. 143
Author(s):  
Irena Steele ◽  
Daniel Allright ◽  
Roger Deutsch
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Nutrient Deficiency ◽  
Redox Status ◽  
Oxidative Stress Response ◽  
Immune Reactivity ◽  
Micronutrient Deficiencies ◽  
Immune Functions ◽  
Food Sensitivity ◽  
Food Antigens

Background: Malnutrition due to insufficient intake of micronutrients, or due to impaired delivery of micronutrients to patients’ cells, is suppressing immune functions that are fundamental to host protection. Concurrently, an excessive triggering of patients’ immune reactions as the result of adverse responses to certain food antigens, can also lead to various chronic health conditions.Objective: To examine nutritional and immunological status in patients’ groups varying in age, dietary regimens and gastrointestinal condition; and explore a possible correlation between an impaired patients’ immune status and micronutrient deficiencies, food sensitivity and oxidative stress responses.Methods: This is a population-based study consisting of a American residents, age 13 and older, who completed the investigator’s provided questionnaires with application of cell-based individualized functional assays. Data for this paper were collected from 845 individuals between May and September 2019, as part of CSS CNA beta study. Micronutrient deficiencies, immune Redox status, antioxidative responses and food sensitivity profiles were assessed for each patient participating in this study.Results: The group of patients with low Redox status demonstrated significantly higher percent of immune reactivity (17%) to food antigens as compared to15% reactivity detected in the groups with the average and strong Redox response. An average number of identified micronutrient deficiencies, as well as beneficial anti-oxidative protective compounds, was also significantly higher in the group with the weak immune function as compared to other two groups.Conclusion: This study suggests that high food sensitivity is associated with a higher nutrient deficiency, a stronger oxidative stress response and a lower immune redox status. 

scholarly journals Lead Drives Complex Dynamics of a Conjugative Plasmid in a Bacterial Community

2021 ◽  
Vol 12 ◽  
Author(s):  
Valentine Cyriaque ◽  
Jonas Stenløkke Madsen ◽  
Laurence Fievez ◽  
Baptiste Leroy ◽  
Lars H. Hansen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Complex Dynamics ◽  
Lead Concentration ◽  
Metal Resistance ◽  
Oxidative Stress Response ◽  
Conjugative Plasmid ◽  
Control Plasmid ◽  
Spread Dynamics ◽  
The Impact

Plasmids carrying metal resistance genes (MRGs) have been suggested to be key ecological players in the adaptation of metal-impacted microbial communities, making them promising drivers of bio-remediation processes. However, the impact of metals on plasmid-mediated spread of MRGs through selection, plasmid loss, and transfer is far from being fully understood. In the present study, we used two-member bacterial communities to test the impact of lead on the dispersal of the IncP plasmid pKJK5 from a Pseudomonas putida KT2440 plasmid donor and two distinct recipients, Variovorax paradoxus B4 or Delftia acidovorans SPH-1 after 4 and 10 days of mating. Two versions of the plasmid were used, carrying or not carrying the lead resistance pbrTRABCD operon, to assess the importance of fitness benefit and conjugative potential for the dispersal of the plasmid. The spread dynamics of metal resistance conveyed by the conjugative plasmid were dependent on the recipient and the lead concentration: For V. paradoxus, the pbr operon did not facilitate neither lead resistance nor variation in plasmid spread. The growth gain brought by the pbr operon to D. acidovorans SPH-1 and P. putida KT2440 at 1 mM Pb enhanced the spread of the plasmid. At 1.5 mM Pb after 4 days, the proteomics results revealed an oxidative stress response and an increased abundance of pKJK5-encoded conjugation and partitioning proteins, which most likely increased the transfer of the control plasmid to D. acidovorans SPH-1 and ensured plasmid maintenance. As a consequence, we observed an increased spread of pKJK5-gfp. Conversely, the pbr operon reduced the oxidative stress response and impeded the rise of conjugation- and partitioning-associated proteins, which slowed down the spread of the pbr carrying plasmid. Ultimately, when a fitness gain was recorded in the recipient strain, the spread of MRG-carrying plasmids was facilitated through positive selection at an intermediate metal concentration, while a high lead concentration induced oxidative stress with positive impacts on proteins encoding plasmid conjugation and partitioning.

scholarly journals Oxidative Stress Response Tips the Balance in Aspergillus terreus Amphotericin B Resistance

2017 ◽  
Vol 61 (10) ◽  
Author(s):  
Emina Jukic ◽  
Michael Blatzer ◽  
Wilfried Posch ◽  
Marion Steger ◽  
Ulrike Binder ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Amphotericin B ◽  
Aspergillus Terreus ◽  
Expression Profiles ◽  
Oxidative Stress Response ◽  
Mrna Levels ◽  
Sod Activity ◽  
Content Type ◽  
The Impact

ABSTRACT In this study, we characterize the impact of antioxidative enzymes in amphotericin B (AmB)-resistant (ATR) and rare AmB-susceptible (ATS) clinical Aspergillus terreus isolates. We elucidate expression profiles of superoxide dismutase (SOD)- and catalase (CAT)-encoding genes, enzymatic activities of SODs, and superoxide anion production and signaling pathways involved in the oxidative stress response (OSR) in ATS and ATR strains under AmB treatment conditions. We show that ATR strains possess almost doubled basal SOD activity compared to that of ATS strains and that ATR strains exhibit an enhanced OSR, with significantly higher sod2 mRNA levels and significantly increased cat transcripts in ATR strains upon AmB treatment. In particular, inhibition of SOD and CAT proteins renders resistant isolates considerably susceptible to the drug in vitro. In conclusion, this study shows that SODs and CATs are crucial for AmB resistance in A. terreus and that targeting the OSR might offer new treatment perspectives for resistant species.

Canalicular Mrp2 localization is reversibly regulated by the intracellular redox status

2008 ◽  
Vol 295 (5) ◽  
pp. G1035-G1041 ◽  
Author(s):  
Shuichi Sekine ◽  
Kousei Ito ◽  
Toshiharu Horie
Keyword(s):  
Oxidative Stress ◽  
Rat Hepatocytes ◽  
Redox Status ◽  
Intracellular Camp ◽  
Isolated Rat Hepatocytes ◽  
Tertiary Butyl ◽  
Canalicular Membrane ◽  
Internalization Process ◽  
Intracellular Redox Status ◽  
Intracellular Redox

Oxidative stress is known to be a common feature of cholestatic syndrome. We have described the internalization of multidrug resistance-associated protein 2 (Mrp2), a biliary transporter involved in bile salt-independent bile flow, under acute oxidative stress, and a series of signaling pathways finally leading to the activation of novel protein kinase C were involved in this mechanism; however, it has been unclear whether the internalized Mrp2 localization was relocalized to the canalicular membrane when the intracellular redox status was recovered from oxidative stress. In this study, we demonstrated that decreased canalicular expression of Mrp2 induced by tertiary-butyl hydroperoxide (t-BHP) was recovered to the canalicular membrane by the replenishment of GSH by GSH-ethyl ester, a cell-permeable form of GSH. Moreover, pretreatment of isolated rat hepatocytes with colchicine and PKA inhibitor did not affect the t-BHP-induced Mrp2 internalization process but did prevent the Mrp2 recycling process induced by GSH replenishment. Moreover, intracellular cAMP concentration similarly changed with the change of intracellular GSH content. Taken together, our data clearly indicate that the redox-sensitive balance of PKA/PKC activation regulates the reversible Mrp2 localization in two different pathways, the microtubule-independent internalization pathway and -dependent recycling pathway of Mrp2.

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