scholarly journals Roles of FadRACB system in formaldehyde detoxification, oxidative stress alleviation and antibiotic susceptibility in Stenotrophomonas maltophilia

Author(s):  
Li-Hua Li ◽  
Cheng-Mu Wu ◽  
Yi-Tsung Lin ◽  
Sz-Yun Pan ◽  
Tsuey-Ching Yang

Abstract Background Formaldehyde toxicity is invariably stressful for microbes. Stenotrophomonas maltophilia, a human opportunistic pathogen, is widely distributed in different environments and has evolved an array of systems to alleviate various stresses. Objectives To characterize the role of the formaldehyde detoxification system FadRACB of S. maltophilia in formaldehyde detoxification, oxidative stress alleviation and antibiotic susceptibility. Methods Presence of the fadRACB operon was verified by RT–PCR. Single or combined deletion mutants of the fadRACB operon were constructed for functional assays. Formaldehyde, menadione and quinolone susceptibilities were assessed by observing cell viability in formaldehyde-, menadione- and quinolone-containing media, respectively. Susceptibility to hydrogen peroxide was evaluated by disc diffusion assay. The agar dilution method was used to assess bacterial antibiotic susceptibilities. Expression of fadRACB was assessed by quantitative RT–PCR. Results The fadR, fadA, fadC and fadB genes were arranged in an operon. Mutants of fadA and/or fadB were more susceptible to formaldehyde and oxidative stress than the WT KJ strain of S. maltophilia. No significant difference was observed in the ability of a fadC single mutant to ameliorate formaldehyde and oxidative stress; however, simultaneous inactivation of fadA, fadB and fadC further enhanced susceptibility to formaldehyde and oxidative stress. In addition, compared with WT KJ, the triple mutant KJΔFadACB was more susceptible to quinolones and more resistant to aminoglycosides. FadR functions as a repressor for the fadRACB operon. The FadRACB operon has moderate expression in aerobically grown WT KJ and is further derepressed by formaldehyde challenge or oxidative stress, but not by antibiotics. Conclusions The FadACB system contributes to mitigation of formaldehyde toxicity and oxidative stress and cross-protects S. maltophilia from quinolones.

2010 ◽  
Vol 55 (2) ◽  
pp. 806-812 ◽  
Author(s):  
Ji-Hoi Moon ◽  
Jae-Hong Park ◽  
Jin-Yong Lee

ABSTRACTPolyphosphate [poly(P)] has antibacterial activity against various Gram-positive bacteria. In contrast, Gram-negative bacteria are generally resistant to poly(P). Here, we describe the antibacterial characterization of poly(P) against a Gram-negative periodontopathogen,Porphyromonas gingivalis. The MICs of pyrophosphate (Na4P2O7) and all poly(P) (Nan+ 2PnO3n+ 1;n= 3 to 75) tested for the bacterium by the agar dilution method were 0.24% and 0.06%, respectively. Orthophosphate (Na2HPO4) failed to inhibit bacterial growth. Poly-P75 was chosen for further study. In liquid medium, 0.03% poly-P75 was bactericidal againstP. gingivalisirrespective of the growth phase and inoculum size, ranging from 105to109cells/ml. UV-visible spectra of the pigments fromP. gingivalisgrown on blood agar with or without poly-P75 showed that poly-P75 reduced the formation of μ-oxo bisheme by the bacterium. Poly-P75 increased hemin accumulation on theP. gingivalissurface and decreased energy-driven uptake of hemin by the bacterium. The expression of the genes encoding hemagglutinins, gingipains, hemin uptake loci, chromosome replication, and energy production was downregulated, while that of the genes related to iron storage and oxidative stress was upregulated by poly-P75. The transmission electron microscope showed morphologically atypical cells with electron-dense granules and condensed nucleoid in the cytoplasm. Collectively, poly(P) is bactericidal againstP. gingivalis, in which hemin/heme utilization is disturbed and oxidative stress is increased by poly(P).


2021 ◽  
Author(s):  
Xiuheng Xue ◽  
Chunhuan Ren ◽  
Luping Wang ◽  
Mengzhu Xu Xu ◽  
Caiyun Fan ◽  
...  

Abstract Background: As global temperatures rise, heat stress has become one of the major environmental stressors in the poultry industry. The purpose of the study was to investigate the effects of heat stress on immune function and oxidative stress, and further reveal the possible mechanisms of oxidative stress induced by heat stress for thymus and spleen of broilers. Methods: At the age of 28 days, thirty broilers were randomly divided into the control group (25 ± 2°C; 24 h/day) and the heat stress group (36 ± 2°C; 8 h/day); the experience was lasted for 1 week. At the end of the experience, the broilers per group were respectively euthanized and collected some samples, then to be analyzed. Results: The results showed that the levels of heat shock proteins 70 (HSP70,P< 0.01), corticosterone (CORT,P< 0.01), the contents of malondialdehyde (MDA, P< 0.05), interleukin-6 (IL-6, P< 0.01) and tumor necrosis factor-alpha (TNF-α, P< 0.01) in serum were significantly higher in heat stress group than that in the control group; The activities of total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) and contents of glutathione (GSH) in heat stress group significantly reduced (P< 0.05) in serum. Compared with the control group, the birds subjected to heat stress reduced the weight (P< 0.01) and the indices of thymus (P< 0.01), the activities of T-AOC (P< 0.01) and SOD (P< 0.05) of spleen, and levels of IL-10 (P< 0.05) and the GSH-PX (P< 0.05) in thymus and spleen, and increased the IL-6 content of thymus (P< 0.05), the MDA content (P< 0.01), and the reactive oxygen species (ROS) levels (P< 0.01) in thymus and spleen. Moreover, the expression of immunoglobulin G (IgG) gene in thymus and spleen of heat stressed broiler significantly increased by reverse transcription-polymerase chain reaction (RT-PCR) and real time RT-PCR (qRT-PCR; P< 0.05); However, the expression of immunoglobulin M (IgM) gene in spleen significantly increased (P< 0.05), and had no significant difference (P> 0.05) in thymus of heat-stressed broiler. Furthermore, the relative expression of ATP binding cassette subfamily G member 2 (ABCG2) in thymus and spleen (P< 0.05), sodium dependent vitamin C transporter-2 (SVCT-2, P< 0.01) and mitochondria calcium uniporter (MCU, P< 0.01) mRNA in thymus of heat stressed broilers significantly increased; and the expression of ABCG2 (P< 0.05), SVCT-2 (P< 0.01) and MCU (P< 0.01) protein of thymus and spleen in the heat-stressed broiler increased significantly compared with the control group. Conclusions: In summary, the study confirmed that heat stress caused oxidative stress to immune organs of broilers, further reduced immune function. Moreover, the potential mechanisms of heat stress-induced oxidative stress for thymus and spleen was further reveal in broilers.


Pharmacology ◽  
2021 ◽  
pp. 1-11
Author(s):  
Naseratun Nessa ◽  
Miyuki Kobara ◽  
Hiroe Toba ◽  
Tetsuya Adachi ◽  
Toshiro Yamamoto ◽  
...  

Introduction: Periodontitis is a lifestyle-related disease that is characterized by chronic inflammation in gingival tissue. Febuxostat, a xanthine oxidase inhibitor, exerts anti-inflammatory and antioxidant effects. Objective: The present study investigated the effects of febuxostat on periodontitis in a rat model. Methods: Male Wistar rats were divided into 3 groups: control, periodontitis, and febuxostat-treated periodontitis groups. Periodontitis was induced by placing a ligature wire around the 2nd maxillary molar and the administration of febuxostat (5 mg/kg/day) was then initiated. After 4 weeks, alveolar bone loss was assessed by micro-computed tomography and methylene blue staining. The expression of osteoprotegerin (OPG), a bone resorption inhibitor, was detected by quantitative RT-PCR and immunological staining, and the number of osteoclasts in gingival tissue was assessed by tartrate-resistant acid phosphatase staining. The mRNA and protein expression levels of the proinflammatory cytokines, tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β), in gingival tissue were measured using quantitative RT-PCR and immunological staining. Oxidative stress in gingival tissue was evaluated by the expression of 4-hydroxy-2-nonenal (4-HNE), and 8-hydroxy-2-deoxyguanosine (8-OHdG). To clarify the systemic effects of periodontitis, blood pressure and glucose tolerance were examined. Results: In rats with periodontitis, alveolar bone resorption was associated with reductions in OPG and increases in osteoclast numbers. The gingival expression of TNF-α, IL-1β, 4-HNE, and 8-OHdG was up-regulated in rats with periodontitis. Febuxostat significantly reduced alveolar bone loss, proinflammatory cytokine levels, and oxidative stress. It also attenuated periodontitis-induced glucose intolerance and blood pressure elevations. Conclusion: Febuxostat prevented the progression of periodontitis and associated systemic effects by inhibiting proinflammatory mediators and oxidative stress.


2021 ◽  
Vol 7 (1) ◽  
pp. 42-50
Author(s):  
Zahra Nazari Barchestani ◽  
◽  
Maryam Rafieirad ◽  

Background: Ischemia causes severe neuronal damage and induces oxidative stress, memory impairment, and reduces pain threshold. Herniarin is a powerful antioxidant. Objectives: This study aimed to evaluate the effect of herniarin on memory, pain, and oxidative stress in an ischemia model in male rats. Materials & Methods: In this study, 50 male rats were divided into 5 groups of control, sham, ischemic, and two other ischemic groups, which received herniarin at doses of 150 and 300 mg/kg by gavage for 14 days. Behavioral tests were performed by shuttle box, and Y-maze and pain tests were performed by Tail-Flick test. Then, the rats’ brains were extracted to evaluate lipid peroxidation and measure the levels of thiol and Glutathione Peroxidase (GPX) in the hippocampus and striatum tissues. The results were expressed as Mean±SEM and then analyzed using suitable statistical methods of ANOVA and least significant difference post-hoc test in SPSS V. 20. Results: Herniarin significantly increased the avoidance memory, spatial memory, and pain thresholds of ischemic rats at different concentrations (P<0.001). Besides, the amount of malondialdehyde (MDA) and thiol in the ischemic group increased significantly in comparison to the control group (P<0.001). Also, in the ischemic group, GPX (P<0.001) significantly decreased. Decreased MDA (P<0.001) and thiol (P<0.001) and increased GPX levels were observed with herniarin administration (P<0.01). Conclusion: According to this study’s results, herniarin can remove free radicals and oxidant substances from the brain. Thus, it improves memory and pain thresholds in the brain hypoperfusion ischemia model.


2019 ◽  
Vol 17 (1) ◽  
pp. 49-57
Author(s):  
Amit Kumar ◽  
Sudha Agrawal ◽  
Tapan Kumar Dhali ◽  
Shankar Kumr Majhi

Introduction: The role of free radicals and oxidative damage in the pathophysiology of vitiligo has been documented in recent studies. Antioxidant supplementation has been reported to be useful in the treatment of vitiligo. Objective: To evaluate the role of oral antioxidants supplementation therapy in the treatment of vitiligo by assessing the onset of repigmentation and oxidative stress. Materials and Methods: A total of 80 cases of vitiligo randomized into two groups: antioxidant and placebo comprising 40 patients each and were followed up for 8 weeks for the assessment of onset of repigmentation of vitiliginous lesions as primary outcome.  The activities of Malondialdehyde (MDA), Vitamin C, and Vitamin E in serum and of Catalase (CAT) in erythrocytes of patients at baseline and at end of eight weeks were also assessed by using the spectrophotometric assay. Results: The onset of repigmentation was noted significantly earlier among the anti-oxidant group as compared to the placebo group (p=0.015). At the baseline, between the two groups, no significant difference was found in the different biochemical parameters. However, at the end of 2 months the level of MDA (p<0.001) was found to be significantly lower and that of Vitamin E (p<0.001) and CAT (p=0.005) was significantly higher among the anti-oxidants group as compared to the placebo group. Conclusion: Antioxidant supplementation carried a better response in terms of early onset of repigmentation and significant decrease in the oxidative stress, in the short follow up of two months.


2013 ◽  
Vol 33 (2) ◽  
pp. 175-180 ◽  
Author(s):  
Hamit Yasar Ellidag ◽  
Esin Eren ◽  
Necat Yilmaz ◽  
Asli Bayindir

Summary Background: Impaired oxidative/antioxidative balance plays an important role in the pathogenesis of many diseases, including cancer. The aim of this study was to evaluate the levels of the novel marker ischemia modified albumin (IMA) and albumin adjusted-IMA (Adj-IMA) in patients with multi- ple myeloma (MM) as well as its association with total antiox- idant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI). Methods: Forty patients with MM (18 females, 22 males; mean age 67.55±8.39 years) and forty age/sex-matched healthy persons (19 females, 21 males; mean age 66.37 ± 6.76 years) were included in this study. Serum levels of IMA, TAS, TOS were analyzed and Adj-IMA and OSI was calcu- lated. Results: Serum IMA, TOS and OSI levels were significantly higher in patients with MM compared to controls (p<0.001 all parameters). There was no significant difference for serum albumin-adjusted IMA and TAS levels between groups (p=0.83 and p=0.17 respectively). Conclusions: In this study, an impaired oxidative/antioxidant status in favor of oxidative stress was found in MM patients. This observation was not confirmed by Adj-IMA calculation. Further studies are needed to establish the relationship of IMA and oxidative stress parameters in multiple myeloma and their relationship to MM and other cancers.


2016 ◽  
Vol 21 (6) ◽  
pp. 487-493 ◽  
Author(s):  
İbrahim Fatih Karababa ◽  
Sermin Nur Savas ◽  
Sehabettin Selek ◽  
Erdinc Cicek ◽  
Esra Ismet Cicek ◽  
...  

Objective: In our study, we aimed to evaluate the plasma homocysteine levels and oxidative stress parameters in patients with adult ADHD (A-ADHD). Method: Blood samples were taken from 32 A-ADHD patients and 32 controls enrolled in the study and plasma homocysteine, serum folate, vitamin B12, total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) were determined. Results were compared between the groups. Results: Patients’ plasma homocysteine level was significantly lower and serum folate level was significantly higher than the controls. The means of plasma homocysteine and folate levels were statistically significantly different between the groups ( p < .05). However, a statistically significant difference was not detected between groups for mean serum vitamin B12, TAS, TOS, and OSI levels ( p > .05). Conclusion: Our study suggests that oxidative balance is not impaired in A-ADHD, and contrary to other psychiatric disorders, homocysteine levels were found to be lower.


2013 ◽  
Vol 6 (2) ◽  
pp. 89-93
Author(s):  
Maya P. Danovska ◽  
Margarita L. Alexandrova ◽  
Irena I. Gencheva

Summary Individuals with hypertension and diabetes mellitus are at high risk of cerebrovascular and cardiovascular morbidity and mortality. Recent advances in the multifactorial pathophysiology of atherogenesis provide important information about the complex interrelations between traditional risk factors, inflammation and oxidative stress in mediating all stages of atherosclerosis. The objective of the study was to determine if some inflammatory and oxidative stress markers in patients with arterial hypertension and diabetes mellitus differ from those in healthy age-matched controls. Our results revealed a significant difference in blood pro/antioxidant activities in hypertensive diabetics and the controls. The investigation of inflammatory and oxidative stress markers along with traditional risk factors proves useful in complex assessment of vascular risk and primary prophylaxis of cerebrovascular and cardiovascular events.


Sign in / Sign up

Export Citation Format

Share Document