Involvement of the Leishmania donovani virulence factor A2 in protection against heat and oxidative stress

2012 ◽  
Vol 132 (2) ◽  
pp. 109-115 ◽  
Author(s):  
Laura-Isobel McCall ◽  
Greg Matlashewski

2019 ◽  
Vol 87 (6) ◽  
Author(s):  
Crystal M. Austin ◽  
Siamak Garabaglu ◽  
Christina N. Krute ◽  
Miranda J. Ridder ◽  
Nichole A. Seawell ◽  
...  

ABSTRACTTo persist within the host and cause disease,Staphylococcus aureusrelies on its ability to precisely fine-tune virulence factor expression in response to rapidly changing environments. During an unbiased transposon mutant screen, we observed that disruption of a two-gene operon,yjbIH, resulted in decreased levels of pigmentation and aureolysin (Aur) activity relative to the wild-type strain. Further analyses revealed that YjbH, a predicted thioredoxin-like oxidoreductase, is predominantly responsible for the observedyjbIHmutant phenotypes, though a minor role exists for the putative truncated hemoglobin YjbI. These differences were due to significantly decreased expression ofcrtOPQMNandaur. Previous studies found that YjbH targets the disulfide- and oxidative stress-responsive regulator Spx for degradation by ClpXP. The absence ofyjbHoryjbIresulted in altered sensitivities to nitrosative and oxidative stress and iron deprivation. Additionally, aconitase activity was altered in theyjbHandyjbImutant strains. Decreased levels of pigmentation and aureolysin (Aur) activity in theyjbHmutant were found to be Spx dependent. Lastly, we used a murine sepsis model to determine the effect of theyjbIHdeletion on pathogenesis and found that the mutant was better able to colonize the kidneys and spleens during an acute infection than the wild-type strain. These studies identified changes in pigmentation and protease activity in response to YjbIH and are the first to have shown a role for these proteins during infection.



2013 ◽  
Vol 26 (4) ◽  
pp. 431-441 ◽  
Author(s):  
Liangsheng Xu ◽  
Weidong Chen

Agrobacterium-mediated transformation (AMT) was used to identify potential virulence factors in Sclerotinia sclerotiorum. Screening AMT transformants identified two mutants showing significantly reduced virulence. The mutants showed growth rate, sclerotial formation, and oxalate production similar to that of the wild type. The mutation was due to a single T-DNA insertion at 212 bp downstream of the Cu/Zn superoxide dismutase (SOD) gene (SsSOD1, SS1G_00699). Expression levels of SsSOD1 were significantly increased under oxidative stresses or during plant infection in the wild-type strain but could not be detected in the mutant. SsSOD1 functionally complemented the Cu/Zn SOD gene in a Δsod1 Saccharomyces cerevisiae mutant. The SOD mutant had increased sensitivity to heavy metal toxicity and oxidative stress in culture and reduced ability to detoxify superoxide in infected leaves. The mutant also had reduced expression levels of other known pathogenicity genes such as endo-polygalacturanases sspg1 and sspg3. The functions of SsSOD1 were further confirmed by SsSOD1-deletion mutation. Like the AMT insertion mutant, the SsSOD1-deletion mutant exhibited normal growth rate, sclerotial formation, oxalate production, increased sensitivity to metal and oxidative stress, and reduced virulence. These results suggest that SsSOD1, while not being required for saprophytic growth and completion of the life cycle, plays critical roles in detoxification of reactive oxygen species during host–pathogen interactions and is an important virulence factor of Sclerotinia sclerotiorum.



2014 ◽  
Vol 58 (10) ◽  
pp. 5916-5928 ◽  
Author(s):  
Manoj Kathuria ◽  
Arindam Bhattacharjee ◽  
Koneni V. Sashidhara ◽  
Suriya Pratap Singh ◽  
Kalyan Mitra

ABSTRACTThis study was performed to investigate the mechanistic aspects of cell death induced by a clerodane diterpene (K-09) inLeishmania donovanipromastigotes that was previously demonstrated to be safe and orally active against visceral leishmaniasis (VL). K-09 caused depolarization of the mitochondrion and the generation of reactive oxygen species, triggering an apoptotic response inL. donovanipromastigotes. Mitochondrial dysfunction subsequently resulted in the release of cytochromecinto the cytosol, impairing ATP production. Oxidative stress caused the depletion of reduced glutathione, while pretreatment with antioxidantN-acetyl cysteine (NAC) was able to abrogate oxidative stress. However, NAC failed to restore the mitochondrial membrane potential or intracellular calcium homeostasis after K-09 treatment, suggesting that the generation of oxidative stress is a downstream event relative to the other events. Caspase-3/-7-like protease activity and genomic DNA fragmentation were observed. Electron microscopy studies revealed gross morphological alterations typical of apoptosis, including severe mitochondrial damage, pyknosis of the nucleus, structural disruption of the mitochondrion-kinetoplast complex, flagellar pocket alterations, and the displacement of organelles. Moreover, an increased number of lipid droplets was detected after K-09 treatment, which is suggestive of altered lipid metabolism. Our results indicate that K-09 induces mitochondrial dysfunction and oxidative stress-mediated apoptotic cell death inL. donovanipromastigotes, sharing many features with metazoan apoptosis. These mechanistic insights provide a basis for further investigation toward the development of K-09 as a potential drug candidate for VL.





Author(s):  
Hasan Haci Yeter ◽  
Berfu Korucu ◽  
Elif Burcu Bali ◽  
Ulver Derici

Abstract. Background: The pathophysiological basis of chronic kidney disease and its complications, including cardiovascular disease, are associated with chronic inflammation and oxidative stress. We investigated the effects of active vitamin D (calcitriol) and synthetic vitamin D analog (paricalcitol) on oxidative stress in hemodialysis patients. Methods: This cross-sectional study was composed of 83 patients with a minimum hemodialysis vintage of one year. Patients with a history of any infection, malignancy, and chronic inflammatory disease were excluded. Oxidative markers (total oxidant and antioxidant status) and inflammation markers (C-reactive protein and interleukin-6) were analyzed. Results: A total of 47% (39/83) patients were using active or analog vitamin D. Total antioxidant status was significantly higher in patients with using active or analog vitamin D than those who did not use (p = 0.006). Whereas, total oxidant status and oxidative stress index were significantly higher in patients with not using vitamin D when compared with the patients who were using vitamin D preparation (p = 0.005 and p = 0.004, respectively). On the other hand, total antioxidant status, total oxidant status, and oxidative stress index were similar between patients who used active vitamin D or vitamin D analog (p = 0.6; p = 0.4 and p = 0.7, respectively). Conclusion: The use of active or selective vitamin D analog in these patients decreases total oxidant status and increases total antioxidant status. Also, paricalcitol is as effective as calcitriol in decreasing total oxidant status and increasing total antioxidant status in patients with chronic kidney disease.





2014 ◽  
Vol 17 (5) ◽  
pp. 271 ◽  
Author(s):  
Murat Bicer ◽  
Tunay Senturk ◽  
Murat Yanar ◽  
Ahmet Tutuncu ◽  
Arzu Yilmaztepe Oral ◽  
...  

<strong>Background</strong>: It has been suggested that off-pump coronary<br />artery bypass grafting (CABG) surgery reduces myocardial<br />ischemia-reperfusion injury, postoperative systemic<br />inflammatory response, and oxidative stress. The aim of this<br />study was to measure serum malondialdehyde (MDA), highsensitivity<br />C-reactive protein (hs-CRP), M30, and M65 levels<br />and to investigate the relationship between M30 levels and<br />oxidative stress and inflammation in patients undergoing onand<br />off-pump CABG surgery.<br /><strong>Methods</strong>: Fifty patients were randomly assigned to onpump<br />or off-pump CABG surgery (25 patients off-pump and<br />25 on-pump CABG surgery), and blood samples were collected<br />prior to surgery, and 30 minutes, 60 minutes, 6 hours,<br />and 24 hours after CABG surgery.<br /><strong>Results</strong>: Compared to the on-pump group, serum MDA<br />levels at 30 minutes, 60 minutes, 6 hours, and 24 hours after<br />the CABG surgery were significantly lower in the off-pump<br />group (P = .001, P = .001, P = .001, and P = .001, respectively).<br />Serum M30 levels were found to be elevated in both groups,<br />returning to baseline at 24 hours. When compared to baseline,<br />the hs-CRP level reached its peak at 24 hours at 13.28 ±<br />5.32 mg/dL in the on-pump group, and 15.44 ± 4.02 mg/dL<br />in the off-pump group.<br /><strong>Conclusion</strong>: CABG surgery is associated with an increase<br />in inflammatory markers and serum M30 levels, indicating<br />epithelial/endothelial apoptosis in the early period.



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