Gamma-glutamylcysteine protects ergothioneine-deficient Mycobacterium tuberculosis mutants against oxidative and nitrosative stress

2018 ◽  
Vol 495 (1) ◽  
pp. 174-178 ◽  
Author(s):  
C. Sao Emani ◽  
M.J. Williams ◽  
P.D. Van Helden ◽  
M.J.C. Taylor ◽  
I.J. Wiid ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Nitrosative Stress ◽  
Oxidative And Nitrosative Stress

scholarly journals Dihydrolipoamide Acyltransferase Is Critical for Mycobacterium tuberculosis Pathogenesis

2006 ◽  
Vol 74 (1) ◽  
pp. 56-63 ◽  
Author(s):  
Shuangping Shi ◽  
Sabine Ehrt
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Sodium Nitrite ◽  
Pyruvate Dehydrogenase ◽  
Nitrosative Stress ◽  
Oxidative And Nitrosative Stress ◽  
Retarded Growth ◽  
Mouse Macrophages

ABSTRACT Mycobacterium tuberculosis has evolved to persist in host macrophages, where it faces a nutrient-poor environment and is exposed to oxidative and nitrosative stress. To defend itself against oxidative/nitrosative stress, M. tuberculosis expresses an NADH-dependent peroxidase and peroxynitrite reductase that is encoded by ahpC, ahpD, lpd, and dlaT. In addition to its central role in the peroxynitrite reductase complex, dlaT (Rv2215) also encodes the E2 component of pyruvate dehydrogenase. Here we demonstrate that inactivation of dlaT in the chromosome of H37Rv resulted in a mutant (H37RvΔdlaT) that displayed phenotypes associated with DlaT's role in metabolism and in defense against nitrosative stress. The H37RvΔdlaT strain showed retarded growth in vitro and was highly susceptible to killing by acidified sodium nitrite. Mouse macrophages readily killed intracellular H37RvΔdlaT organisms, and in mice dlaT was required for full virulence.

scholarly journals Silencing of Oxidative Stress Response in Mycobacterium tuberculosis: Expression Patterns of ahpC in Virulent and Avirulent Strains and Effect ofahpC Inactivation

2001 ◽  
Vol 69 (10) ◽  
pp. 5967-5973 ◽  
Author(s):  
B. Springer ◽  
S. Master ◽  
P. Sander ◽  
T. Zahrt ◽  
M. McFalone ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Nitrosative Stress ◽  
Expression Patterns ◽  
Acute Infection ◽  
Cumene Hydroperoxide ◽  
Green Fluorescence Protein ◽  
Normal Growth ◽  
Oxidative And Nitrosative Stress ◽  
Virulent Strains

ABSTRACT Intracellular pathogens such as Mycobacterium tuberculosis are able to survive in the face of antimicrobial products generated by the host cell in response to infection. The product of the alkyl hydroperoxide reductase gene (ahpC) of M. tuberculosis is thought to be involved in protecting the organism against both oxidative and nitrosative stress encountered within the infected macrophage. Here we report that, contrary to expectations, ahpC expression in virulent strains of M. tuberculosis and Mycobacterium bovis grown in vitro is repressed, often below the level of detection, whereas expression in the avirulent vaccine strainM. bovis BCG is constitutively high. The repression of the ahpC gene of the virulent strains is independent of the naturally occurring lesions of central regulatoroxyR. Using a green fluorescence protein vector (gfp)-ahpC reporter construct we present data showing that repression of ahpC of virulentM. tuberculosis also occurred during growth inside macrophages, whereas derepression in BCG was again seen under identical conditions. Inactivation of ahpC on the chromosome ofM. tuberculosis by homologous recombination had no effect on its growth during acute infection in mice and did not affect in vitro sensitivity to H2O2. However, consistent with AhpC function in detoxifying organic peroxides, sensitivity to cumene hydroperoxide exposure was increased in theahpC::Kmr mutant strain. The preservation of a functional ahpC gene in M. tuberculosis in spite of its repression under normal growth conditions suggests that, while AhpC does not play a significant role in establishing infection, it is likely to be important under certain, as yet undefined conditions. This is supported by the observation that repression of ahpC expression in vitro was lifted under conditions of static growth.

scholarly journals Dissecting the RecA-(In)dependent Response to Mitomycin C in Mycobacterium tuberculosis Using Transcriptional Profiling and Proteomics Analyses

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1168
Author(s):  
Anna Brzostek ◽  
Przemysław Płociński ◽  
Alina Minias ◽  
Aneta Ciszewska ◽  
Filip Gąsior ◽  
...  
Keyword(s):  
Dna Damage ◽  
Mycobacterium Tuberculosis ◽  
Mitomycin C ◽  
Nitrosative Stress ◽  
Transcriptional Profiling ◽  
Regulatory System ◽  
Transcript Level ◽  
Reca Gene ◽  
Oxidative And Nitrosative Stress ◽  
Genes Encoding

Mycobacteria exploit at least two independent global systems in response to DNA damage: the LexA/RecA-dependent SOS response and the PafBC-regulated pathway. Intracellular pathogens, such as Mycobacterium tuberculosis, are exposed to oxidative and nitrosative stress during the course of infection while residing inside host macrophages. The current understanding of RecA-independent responses to DNA damage is based on the saprophytic model of Mycobacterium smegmatis, a free-living and nonpathogenic mycobacterium. The aim of the present study was to identify elements of RecA-independent responses to DNA damage in pathogenic intracellular mycobacteria. With the help of global transcriptional profiling, we were able to dissect RecA-dependent and RecA-independent pathways. We profiled the DNA damage responses of an M. tuberculosis strain lacking the recA gene, a strain with an undetectable level of the PafBC regulatory system, and a strain with both systems tuned down simultaneously. RNA-Seq profiling was correlated with the evaluation of cell survival in response to DNA damage to estimate the relevance of each system to the overall sensitivity to genotoxic agents. We also carried out whole-cell proteomics analysis of the M. tuberculosis strains in response to mitomycin C. This approach highlighted that LexA, a well-defined key element of the SOS system, is proteolytically inactivated during RecA-dependent DNA repair, which we found to be transcriptionally repressed in response to DNA-damaging agents in the absence of RecA. Proteomics profiling revealed that AlkB was significantly overproduced in the ΔrecA pafBCCRISPRi/dCas9 strain and that Holliday junction resolvase RuvX was a DNA damage response factor that was significantly upregulated regardless of the presence of functional RecA and PafBC systems, thus falling into a third category of DNA damage factors: RecA- and PafBC-independent. While invisible to the mass spectrometer, the genes encoding alkA, dnaB, and dnaE2 were significantly overexpressed in the ΔrecA pafBCCRISPRi/dCas9 strain at the transcript level.

scholarly journals Myeloperoxidase-Related Chlorination Activity Is Positively Associated with Circulating Ceruloplasmin in Chronic Heart Failure Patients: Relationship with Neurohormonal, Inflammatory, and Nutritional Parameters

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Aderville Cabassi ◽  
Simone Maurizio Binno ◽  
Stefano Tedeschi ◽  
Gallia Graiani ◽  
Cinzia Galizia ◽  
...  
Keyword(s):  
Heart Failure ◽  
Nitrosative Stress ◽  
Defense Mechanism ◽  
Nyha Class ◽  
Protein Nitration ◽  
Class Iii ◽  
Oxidative And Nitrosative Stress ◽  
Radical Production ◽  
Antioxidant Function ◽  
The Relationship

Rationale. Heart failure (HF) is accompanied by the development of an imbalance between oxygen- and nitric oxide-derived free radical production leading to protein nitration. Both chlorinating and peroxidase cycle of Myeloperoxidase (MPO) contribute to oxidative and nitrosative stress and are involved in tyrosine nitration of protein. Ceruloplasmin (Cp) has antioxidant function through its ferroxidase I (FeOxI) activity and has recently been proposed as a physiological defense mechanism against MPO inappropriate actions.Objective. We investigated the relationship between plasma MPO-related chlorinating activity, Cp and FeOxI, and nitrosative stress, inflammatory, neurohormonal, and nutritional biomarkers in HF patients.Methods and Results. In chronic HF patients (n=81, 76±9 years, NYHA Class II (26); Class III (29); Class IV (26)) and age-matched controls (n=17, 75±11 years, CTR), plasma MPO chlorinating activity, Cp, FeOxI, nitrated protein, free Malondialdehyde, BNP, norepinephrine, hsCRP, albumin, and prealbumin were measured. Plasma MPO chlorinating activity, Cp, BNP, norepinephrine, and hsCRP were increased in HF versus CTR. FeOxI, albumin, and prealbumin were decreased in HF. MPO-related chlorinating activity was positively related to Cp (r= 0.363,P<0.001), nitrated protein, hsCRP, and BNP and inversely to albumin.Conclusions. Plasma MPO chlorinated activity is increased in elderly chronic HF patients and positively associated with Cp, inflammatory, neurohormonal, and nitrosative parameters suggesting a role in HF progression.

scholarly journals Methane and Inflammation - A Review (Fight Fire with Fire)

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Marietta Zita Poles ◽  
László Juhász ◽  
Mihály Boros
Keyword(s):  
Stress Responses ◽  
Nitrosative Stress ◽  
Ischemia Reperfusion ◽  
Signalling Pathways ◽  
Experimental Conditions ◽  
Neuroprotective Effects ◽  
Oxidative And Nitrosative Stress ◽  
Carbohydrate Fermentation ◽  
Insight Into

AbstractMammalian methanogenesis is regarded as an indicator of carbohydrate fermentation by anaerobic gastrointestinal flora. Once generated by microbes or released by a non-bacterial process, methane is generally considered to be biologically inactive. However, recent studies have provided evidence for methane bioactivity in various in vivo settings. The administration of methane either in gas form or solutions has been shown to have anti-inflammatory and neuroprotective effects in an array of experimental conditions, such as ischemia/reperfusion, endotoxemia and sepsis. It has also been demonstrated that exogenous methane influences the key regulatory mechanisms and cellular signalling pathways involved in oxidative and nitrosative stress responses. This review offers an insight into the latest findings on the multi-faceted organ protective activity of exogenous methane treatments with special emphasis on its versatile effects demonstrated in sepsis models.

scholarly journals The role of oxidative and nitrosative stress in the pathology of osteoarthritis: Novel candidate biomarkers for quantification of degenerative changes in the knee joint

2018 ◽  
Vol 10 (2) ◽  
Author(s):  
Alexander Franz ◽  
Laura Joseph ◽  
Constantin Mayer ◽  
Jan-Frieder Harmsen ◽  
Holger Schrumpf ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Synovial Fluid ◽  
Knee Joint ◽  
Human Serum ◽  
Synovial Membrane ◽  
Nitrosative Stress ◽  
Control Groups ◽  
Oxidative And Nitrosative Stress ◽  
And Oxidative Stress

Osteoarthritis (OA) is the most frequently diagnosed joint disorder worldwide with increasing prevalence and crucial impact on the quality of life of affected patients through chronic pain, decreasing mobility and invalidity. Although some risk factors, such as age, obesity and previous joint injury are well established, the exact pathogenesis of OA on a cellular and molecular level remains less understood. Today, the role of nitrosative and oxidative stress has not been investigated conclusively in the pathogenesis of OA yet. Therefore, the objective of this study was to identify biological substances for oxidative and nitrosative stress, which mirror the degenerative processes in an osteoarthritic joint. 69 patients suffering from a diagnosed knee pain participated in this study. Based on the orthopedic diagnosis, patients were classified into an osteoarthritis group (OAG, n=24) or in one of two control groups (meniscopathy, CG1, n=11; anterior cruciate ligament rupture, CG2, n=34). Independently from the study protocol, all patients underwent an invasive surgical intervention which was used to collect samples from the synovial membrane, synovial fluid and human serum. Synovial biopsies were analyzed histopathologically for synovitis (Krenn-Score) and immunohistochemically for detection of end products of oxidative (8-isoprostane F2α) and nitrosative (3-nitrotyrosine) stress. Additionally, the fluid samples were analyzed for 8-isoprostane F2α and 3-nitrotyrosine by competitive ELISA method. The analyzation of inflammation in synovial biopsies revealed a slight synovitis in all three investigated groups. Detectable concentrations of 3-nitrotyrosine were reported in all three investigated groups without showing any significant differences between the synovial biopsies, fluid or human serum. In contrast, significant increased concentrations of 8-isoprostane F2α were detected in OAG compared to both control groups. Furthermore, our data showed a significant correlation between the histopathological synovitis and oxidative stress in OAG (r=0.728, P<0.01). There were no significant differences between the concentrations of 8-isoprostane F2α in synovial fluid and human serum. The findings of the current study support the hypothesis that oxidative and nitrosative stress are components of the multi-factory pathophysiological formation of OA. It seems reasonable that an inflammatory process in the synovial membrane triggers the generation of oxidative and nitrosative acting substances which can lead to a further degradation of the articular cartilage. Based on correlations between the observed degree of inflammation and investigated biomarkers, especially 8-isoprostane F2α seems to be a novel candidate biomarker for OA. However, due to the finding that also both control groups showed increased concentrations of selected biomarkers, future studies have to validate the diagnostic potential of these biomarkers in OA and in related conditions of the knee joint.

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