Ciprofloxacin interferes with Salmonella Typhimurium intracellular survival and host virulence through repression of Salmonella pathogenicity island-2 (SPI-2) genes expression

2020 ◽  
Vol 78 (1) ◽  
Author(s):  
Momen Askoura ◽  
Wael Abdel Halim Hegazy
Keyword(s):  
Intracellular Survival ◽  
Inhibitory Effect ◽  
Expression Of Genes ◽  
Type Three Secretion System ◽  
Genes Expression ◽  
Gentamicin Protection Assay ◽  
Infection Models ◽  
Genes Encoding ◽  
Resistance Patterns ◽  
Host Infection

ABSTRACT Current study aims to characterize the influence of sub-minimum inhibitory concentration (sub-MIC) of ciprofloxacin on Salmonella intracellular survival and host virulence. Herein, Salmonella resistance patterns to various antibiotics were in agreement with those reported in previous studies. Moreover, intracellular survival of both ciprofloxacin-sensitive and -resistant Salmonella was markedly reduced upon treatment with sub-MIC of ciprofloxacin as determined by gentamicin protection assay. These findings were further confirmed using immunostaining indicating an inhibitory effect of sub-MIC of ciprofloxacin on Salmonella intracellular survival. RT-qPCR revealed that expression of genes encoding Salmonella type three secretion system (TTSS) decreased upon bacterial exposure to sub-MIC of ciprofloxacin. Furthermore, bacterial exposure to sub-MIC of ciprofloxacin significantly reduced expression of both sifA and sifB, which are important for Salmonella filaments formation within the host. Treatment of Salmonella with sub-MIC of ciprofloxacin reduced bacterial capacity to kill mice infection models. A lower mortality rate was observed in mice injected with Salmonella treated with sub-MIC of ciprofloxacin as compared with mice inoculated with untreated bacteria. Collectively, current findings indicate that, in addition to its bactericidal potential, sub-MIC of ciprofloxacin could inhibit Salmonella intracellular survival, virulence genes expression as well as host pathogenesis, providing another mechanism for ciprofloxacin in limiting Salmonella host infection.

scholarly journals Expression of genes encoding IGFBPs, SNARK, CD36, and PECAM1 in the liver of mice treated with chromium disilicide and titanium nitride nanoparticles

2017 ◽  
Vol 51 (2) ◽  
pp. 84-95
Author(s):  
Dmytro O. Minchenko ◽  
D. O. Tsymbal ◽  
O. P. Yavorovsky ◽  
N. V. Solokha ◽  
O. H. Minchenko
Keyword(s):  
Titanium Nitride ◽  
Mouse Liver ◽  
Quantitative Polymerase Chain Reaction ◽  
Down Regulation ◽  
Expression Of Genes ◽  
Genes Expression ◽  
Genes Encoding ◽  
Polymerase Chain ◽  
Working Day ◽  
20 Nm

AbstractObjective. The aim of the present study was to examine the effect of chromium disilicide and titanium nitride nanoparticles on the expression level of genes encoding important regulatory factors (IGFBP1, IGFBP2, IGFBP3, IGFBP4, IGFBP5, SNARK/NUAK2, CD36, and PECAM1/CD31) in mouse liver for evaluation of possible toxic effects of these nanoparticles.Methods. Male mice received 20 mg chromium disilicide nanoparticles (45 nm) and titanium nitride nanoparticles (20 nm) with food every working day for 2 months. The expression of IGFBP1, IGFBP2, IGFBP3, IGFBP4, IGFBP5, SNARK, CD36, and PECAM1 genes in mouse liver was studied by quantitative polymerase chain reaction.Results. Treatment of mice with chromium disilicide nanoparticles led to down-regulation of the expression of IGFBP2, IGFBP5, PECAM1, and SNARK genes in the liver in comparison with control mice, with more prominent changes for SNARK gene. At the same time, the expression of IGFBP3 and CD36 genes was increased in mouse liver upon treatment with chromium disilicide nanoparticles. We have also shown that treatment with titanium nitride nanoparticles resulted in down-regulation of the expression of IGFBP2 and SNARK genes in the liver with more prominent changes for SNARK gene. At the same time, the expression of IGFBP3, IGFBP4, and CD36 genes was increased in the liver of mice treated with titanium nitride nanoparticles. Furthermore, the effect of chromium disilicide nanoparticles on IGFBP2 and CD36 genes expression was significantly stronger as compared to titanium nitride nanoparticles.Conclusions. The results of this study demonstrate that chromium disilicide and titanium nitride nanoparticles have variable effects on the expression of IGFBP2, IGFBP3, IGFBP4, IGFBP5, SNARK, CD36, and PECAM1 genes in mouse liver, which may reflect the genotoxic activities of the studied nanoparticles.

scholarly journals Comparative Metabolomic Analysis Reveals Distinct Flavonoid Biosynthesis Regulation for Leaf Color Development of Cymbidium sinense ‘Red Sun’

2020 ◽  
Vol 21 (5) ◽  
pp. 1869 ◽  
Author(s):  
Jie Gao ◽  
Rui Ren ◽  
Yonglu Wei ◽  
Jianpeng Jin ◽  
Sagheer Ahmad ◽  
...  
Keyword(s):  
Enzyme Activities ◽  
Biosynthetic Pathway ◽  
Color Change ◽  
Leaf Color ◽  
Anthocyanin Biosynthetic Pathway ◽  
Expression Of Genes ◽  
Genes Expression ◽  
Genes Encoding ◽  
Changing Patterns ◽  
Cymbidium Sinense

The colorful leaf is an important ornamental character of Cymbidium sinense (C. sinense), especially the red leaf, which has always been attracted by breeders and consumers. However, little is documented on the formation mechanism of the red leaf of C. sinense. In this study, the changing patterns of flavonoid-related metabolites, corresponding enzyme activities and genes expression in the leaves of C. sinense ‘Red Sun’ from red to yellow and finally to green was investigated. A total of 196 flavonoid-related metabolites including 11 anthocyanins metabolites were identified using UPLC-MS/MS-based approach. In the process of leaf color change, 42 metabolites were identified as having significantly different contents and the content of 28 differential metabolites turned to zero. In anthocyanin biosynthetic pathway, content of all 15 identified metabolites showed downregulation trend in the process of leaf color change. Among the 15 metabolites, the contents of Naringenin chalcone, Pelargonidin O-acetylhexoside and Anthocyanin 3-O-beta-d-glucoside decreased to zero in the green leaf stage. The changing pattern of enzyme activity of 10 enzymes involved in the anthocyanin biosynthetic pathway showed different trends from red leaves that have turned yellow and finally green, while the expression of genes encoding these enzymes was all down-regulated in the process of leaf color change. The results of this study revealed the types of flavonoid-related metabolites and the comprehensive analysis of metabolites content, enzyme activities and genes expression providing a new reference for breeders to improve the leaf color of C. sinense ‘Red Sun’.

scholarly journals Effect of Acid Adaptation on the Fate of Listeria monocytogenes in THP-1 Human Macrophages Activated by Gamma Interferon

2002 ◽  
Vol 70 (8) ◽  
pp. 4369-4378 ◽  
Author(s):  
Maria Pia Conte ◽  
Gloria Petrone ◽  
Assunta Maria Di Biase ◽  
Catia Longhi ◽  
Michela Penta ◽  
...  
Keyword(s):  
Listeria Monocytogenes ◽  
Cell Invasion ◽  
Acid Resistance ◽  
Intracellular Survival ◽  
Low Ph ◽  
Gamma Interferon ◽  
Acid Adaptation ◽  
Human Macrophages ◽  
Expression Of Genes ◽  
Genes Encoding

ABSTRACT In Listeria monocytogenes the acid tolerance response (ATR) takes place through a programmed molecular response which ensures cell survival under unfavorable conditions. Much evidence links ATR with virulence, but the molecular determinants involved in the reactivity to low pHs and the behavior of acid-exposed bacteria within host cells are still poorly understood. We have investigated the effect of acid adaptation on the fate of L. monocytogenes in human macrophages. Expression of genes encoding determinants for cell invasion and intracellular survival was tested for acid-exposed bacteria, and invasive behavior in the human myelomonocytic cell line THP-1 activated with gamma interferon was assessed. Functional approaches demonstrated that preexposure to an acidic pH enhances the survival of L. monocytogenes in activated human macrophages and that this effect is associated with an altered pattern of expression of genes involved in acid resistance and cell invasion. Significantly decreased transcription of the plcA gene, encoding a phospholipase C involved in vacuolar escape and cell-to-cell spread, was observed in acid-adapted bacteria. This effect was due to a reduction in the quantity of the bicistronic plcA-prfA transcript, concomitant with an increase in the level(s) of the monocistronic prfA mRNA(s). The transcriptional shift from distal to proximal prfA promoters resulted in equal levels of the prfA transcript (and, as a consequence, of the inlA, hly, and actA transcripts) under neutral and acidic conditions. In contrast, the sodC and gad genes, encoding a cytoplasmic superoxide dismutase and the glutamate-based acid resistance system, respectively, were positively regulated at a low pH. Morphological approaches confirmed the increased intracellular survival and growth of acid-adapted L. monocytogenes cells both in vacuoles and in the cytoplasm of interferon gamma-activated THP-1 macrophages. Our data indicate that preexposure to a low pH has a positive impact on subsequent challenge of L. monocytogenes with macrophagic cells.

scholarly journals The glucose metabolite methylglyoxal inhibits expression of the glucose transporter genes by inactivating the cell surface glucose sensors Rgt2 and Snf3 in yeast

2016 ◽  
Vol 27 (5) ◽  
pp. 862-871 ◽  
Author(s):  
Adhiraj Roy ◽  
Salman Hashmi ◽  
Zerui Li ◽  
Angela D. Dement ◽  
Kyu Hong Cho ◽  
...  
Keyword(s):  
Cell Surface ◽  
Glucose Transporter ◽  
Inhibitory Effect ◽  
Glucose Sensors ◽  
Yeast Cells ◽  
Yeast Cell Surface ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Extracellular Glucose ◽  
The Stability

Methylglyoxal (MG) is a cytotoxic by-product of glycolysis. MG has inhibitory effect on the growth of cells ranging from microorganisms to higher eukaryotes, but its molecular targets are largely unknown. The yeast cell-surface glucose sensors Rgt2 and Snf3 function as glucose receptors that sense extracellular glucose and generate a signal for induction of expression of genes encoding glucose transporters ( HXTs). Here we provide evidence that these glucose sensors are primary targets of MG in yeast. MG inhibits the growth of glucose-fermenting yeast cells by inducing endocytosis and degradation of the glucose sensors. However, the glucose sensors with mutations at their putative ubiquitin-acceptor lysine residues are resistant to MG-induced degradation. These results suggest that the glucose sensors are inactivated through ubiquitin-mediated endocytosis and degraded in the presence of MG. In addition, the inhibitory effect of MG on the glucose sensors is greatly enhanced in cells lacking Glo1, a key component of the MG detoxification system. Thus the stability of these glucose sensors seems to be critically regulated by intracellular MG levels. Taken together, these findings suggest that MG attenuates glycolysis by promoting degradation of the cell-surface glucose sensors and thus identify MG as a potential glycolytic inhibitor.

scholarly journals The inhibitory effect of ethanol on Sestrin3 in the pathogenesis of ethanol-induced liver injury

2014 ◽  
Vol 307 (1) ◽  
pp. G58-G65 ◽  
Author(s):  
Xinqin Kang ◽  
Kateryna Petyaykina ◽  
Rongya Tao ◽  
Xiwen Xiong ◽  
X. Charlie Dong ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
Lipid Synthesis ◽  
Inhibitory Effect ◽  
Hairpin Rna ◽  
Triglyceride Accumulation ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Ethanol Feeding ◽  
Regulate Lipid Metabolism

Sestrins ( Sesns) are a family of stress-sensitive genes that have been suggested to regulate lipid metabolism. Chronic ethanol feeding is known to cause lipid accumulation in hepatocytes. This study was designed to investigate the role of S esn3 in the pathogenesis of alcohol-induced hepatic steatosis. We demonstrated that ethanol inhibited the expression of Sesn3 in VL-17A cells. Overexpression of Sesn3 ameliorated triglyceride accumulation; downregulation using short hairpin RNA significantly deteriorated triglyceride accumulation in these cells. The expression of Sesn3 was also reduced in mice fed with ethanol for 4 wk. Overexpression of Sesn3 prevented hepatic steatosis, whereas knockdown of Sesn3 worsened hepatic steatosis in ethanol-fed mice. Overexpression of Sesn3 significantly reduced the expression of genes encoding for lipid synthesis through AMPK pathway. Overexpression of Sesn3 augmented the effect of ethanol on phospho-p70 S6 kinase. The levels of hepatic light chain 3, a marker for autophagy, expression were significantly decreased in ethanol-fed mice after Sesn3 gene was knocked down. Our findings suggest that inhibitory effect of ethanol on Sesn3 may play an important role in the development of ethanol-induced fatty liver.

scholarly journals Effect of six weeks 1000 mg/day vitamin C supplementation and healthy training in elderly women on genes expression associated with the immune response - a randomized controlled trial

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Małgorzata Żychowska ◽  
Agata Grzybkowska ◽  
Mariusz Zasada ◽  
Anna Piotrowska ◽  
Danuta Dworakowska ◽  
...  
Keyword(s):  
Immune Response ◽  
Vitamin C ◽  
Body Mass ◽  
Elderly Women ◽  
Controlled Trial ◽  
Expression Of Genes ◽  
Genes Expression ◽  
Vitamin C Supplementation ◽  
Group A ◽  
Adaptation To Training

Abstract Background In this study, we investigated the effects of supplementation and exercise on the expression of genes associated with inflammation like CCL2, CRP, IL1, IL6, IL10 mRNA in elderly women. Methods Twenty four participants divided randomly into two groups were subjected to 6 weeks of the same health training program (three times per week). SUP group (supplemented, n = 12, mean age 72.8 ± 5.26 years and mean body mass 68.1 ± 8.3 kg) received 1000 mg of Vitamin C/day during the training period, while CON group (control, n = 12, mean age 72.4 ± 5.5 years and body mass 67.7 ± 7.5 kg) received placebo. Results No significant changes in IL-1, IL-6, IL-10 and CRP mRNA were observed within and between groups. However, there was a clear tendency of a decrease in IL-6 (two-way ANOVA, significant between investigated time points) and an increase in IL-10 mRNA noted in the supplemented group. A significant decrease in CCL2 mRNA was observed only in the CON group (from 2^0.2 to 2^0.1, p = 0.01). Conclusions It can be concluded, that 6 weeks of supplementation and exercise was too short to obtain significant changes in gene expression in leukocytes, but supplementation of 1000 mg vitamin C positively affected IL-6 and IL-10 expression – which are key changes in the adaptation to training. However, changes in body mass, IL1 and CCL2 were positive in CON group. It is possible that Vitamin C during 6 weeks of supplementation could have different effects on the expression of individual genes involved in the immune response. Trial registration Retrospectively registered. 

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