scholarly journals Specific NDM-1 Inhibitor of Isoliquiritin Enhances the Activity of Meropenem against NDM-1-positive Enterobacteriaceae in vitro

2020 ◽  
Vol 17 (6) ◽  
pp. 2162
Author(s):  
Yanling Wang ◽  
Xiaodi Sun ◽  
Fanrong Kong ◽  
Lining Xia ◽  
Xuming Deng ◽  
...  
Keyword(s):  
Antibacterial Effect ◽  
Specific Inhibitor ◽  
Inhibitory Effect ◽  
Therapeutic Effects ◽  
New Delhi ◽  
E Coli ◽  
Class B ◽  
Time Kill ◽  
Growth Of Bacteria

NDM-1-positive Enterobacteriaceae have caused serious clinical infections, with high mortality rates. Carbapenem was the ultimate expectation for the treatment of such infections in clinical practice. However, since the discovery of plasmid-mediated New Delhi metallo-β-lactamase-1 (NDM-1), the efficient therapeutic effects of carbapenems have been increasingly restricted. Here, we identified isoliquiritin, a novel specific inhibitor of the NDM-1 enzyme that restored the activity of carbapenem against NDM-1-producing E. coli isolates and K. pneumoniae isolates without affecting the growth of bacteria. A checkerboard test, growth curve assays and time-kill assays confirmed the significant synergistic effect of isoliquiritin combined with meropenem in vitro. It is worth noting that isoliquiritin only inhibited the activity of NDM-1 and had no obvious inhibitory effect on other class B metallo-β-lactamases (VIM-1) or NDM-1 mutants (NDM-5). The FIC indices of meropenem with isoliquiritin on NDM-1-positive E. coli and K. pneumoniae were all less than 0.5. Isoliquiritin had no influences on the expression of NDM-1-positive strains at concentrations below 64 µg/mL. Collectively, our results show that isoliquiritin is a potential adjuvant therapy drug that could enhance the antibacterial effect of carbapenems, such as meropenem, on NDM-1-positive Enterobacteria and lay the foundation for subsequent clinical trials.

Combined Inhibitory Effect of Curcuma Xanthorrhiza Extract and Xylitol on Streptococcus Mutans and Actinomyces Viscosus

2007 ◽  
Vol 342-343 ◽  
pp. 861-864
Author(s):  
Hae Sun Kim ◽  
Choong Ho Choi ◽  
H.K. Kwon ◽  
B.I. Kim
Keyword(s):  
Antibacterial Effect ◽  
Bacterial Species ◽  
Inhibitory Effect ◽  
Distilled Water ◽  
Phenol Red ◽  
Ph Indicator ◽  
Bacterial Fermentation ◽  
Curcuma Xanthorrhiza ◽  
Growth Of Bacteria

This study evaluated the combined inhibitory effects of a Curcuma xanthorrhiza extract (CXE) and Xylitol on S. mutans and A. viscosus in vitro. Three series of experiments on S. mutans and A. viscosus were carried out. In the first series, the Minimum inhibitory concentrations (MICs) of CXE, Xylitol, and CXE mixed with Xylitol (CXE+Xylitol) against S. mutans and A. viscosus were determined. Second, the antibacterial effect and the rapid effectiveness of CXE, Xylitol, and CXE+Xylitol against those bacteria was evaluated as contacting for 1, 2, 5, and 10 minutes. Finally, The saccharolytic capability of S. mutans was examined using bovine teeth that had been pretreated with CXE (1%), Xylitol (1%), CXE+Xylitol (1%), chlorhexidine (1%) and distilled water, and rinsed with distilled water. The pretreated bovine teeth were layered with soft agar containing sucrose (5%), S. mutans and phenol red, as a pH indicator, and incubated. The MICs of CXE were 5 ppm on both bacterial species. Xylitol did not inhibit either species. The MICs of CXE+Xylitol were 10 and 5 ppm against S. mutans, A. viscosus, respectively. According to the rapid effectiveness, CXE completely inhibited the growth of bacteria but Xylitol did not. CXE+Xylitol could completely inhibit the growth of bacteria. An evaluation of the saccharolytic capability of S. mutans on bovine teeth revealed that distilled water and Xylitol could not inhibit bacterial fermentation. However, the bovine teeth containing CXE, CXE+Xylitol and chlorhexidine inhibited the fermentation of bacteria. These results show that CXE and CXE+Xylitol have a strong antibacterial effect on S. mutans and A. viscosus in vitro.

scholarly journals Antimicrobial Effects of Minocycline, Tigecycline, Ciprofloxacin, and Levofloxacin against Elizabethkingia anophelis using In Vitro Time-Kill Assays and In Vivo Zebrafish Animal Models

Antibiotics ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 285
Author(s):  
Jiun-Nong Lin ◽  
Chung-Hsu Lai ◽  
Yi-Han Huang ◽  
Chih-Hui Yang
Keyword(s):  
Animal Models ◽  
Antibacterial Activities ◽  
Bactericidal Effect ◽  
Multidrug Resistant ◽  
Inhibitory Effect ◽  
In Vivo Studies ◽  
Therapeutic Effects ◽  
Time Kill

Elizabethkingia anophelis is a multidrug-resistant pathogen. This study evaluated the antimicrobial activity of minocycline, tigecycline, ciprofloxacin, and levofloxacin using in vitro time-kill assays and in vivo zebrafish animal models. The E. anophelis strain ED853-49 was arbitrarily selected from a bacterial collection which was concomitantly susceptible to minocycline, tigecycline, ciprofloxacin, and levofloxacin. The antibacterial activities of single agents at 0.5–4 × minimum inhibitory concentration (MIC) and dual-agent combinations at 2 × MIC using time-kill assays were investigated. The therapeutic effects of antibiotics in E. anophelis-infected zebrafish were examined. Both minocycline and tigecycline demonstrated bacteriostatic effects but no bactericidal effect. Minocycline at concentrations ≥2 × MIC and tigecycline at concentrations ≥3 × MIC exhibited a long-standing inhibitory effect for 48 h. Bactericidal effects were observed at ciprofloxacin and levofloxacin concentrations of ≥3 × MIC within 24 h of initial inoculation. Rapid regrowth of E. anophelis occurred after the initial killing phase when ciprofloxacin was used, regardless of the concentration. Levofloxacin treatment at the concentration of ≥2 × MIC consistently resulted in the long-lasting and sustainable inhibition of bacterial growth for 48 h. The addition of minocycline or tigecycline weakened the killing effect of fluoroquinolones during the first 10 h. The minocycline-ciprofloxacin or minocycline–levofloxacin combinations achieved the lowest colony-forming unit counts at 48 h. Zebrafish treated with minocycline or a combination of minocycline and levofloxacin had the highest survival rate (70%). The results of these in vitro and in vivo studies suggest that the combination of minocycline and levofloxacin is the most effective therapy approach for E. anophelis infection.

scholarly journals Flavone-Rich Fractions and Extracts from Oroxylum indicum and Their Antibacterial Activities against Clinically Isolated Zoonotic Bacteria and Free Radical Scavenging Effects

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1773
Author(s):  
Patchima Sithisarn ◽  
Piyanuch Rojsanga ◽  
Pongtip Sithisarn
Keyword(s):  
Antibacterial Activities ◽  
Inhibitory Effect ◽  
Total Flavonoid ◽  
Total Phenolic ◽  
Antibacterial Effects ◽  
E Coli ◽  
Young Fruit ◽  
Oroxylum Indicum ◽  
Zoonotic Bacteria

Oroxylum indicum extracts from the seeds collected from Lampang and Pattani provinces in Thailand, and young fruits and flowers exhibited in vitro display antioxidant and antibacterial activities against clinically isolated zoonotic bacteria including Staphylococcus intermedius, Streptococcus suis, Pseudomonas aeruginosa, β-hemolytic Escherichia coli and Staphylococcus aureus. The orange crystals and yellow precipitates were obtained from the preparation processes of the seed extracts. The orange-red crystals from the seeds collected from Lampang province exhibited strong in vitro 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging effects (EC50 value = 25.99 ± 3.30 μg/mL) and antibacterial effects on S. intermedius and β-hemolytic E. coli while the yellow precipitate from the same source exhibited only antioxidant activity. Quantitative analysis of phytochemicals in O. indicum samples by spectrophotometric and HPLC techniques showed that they contained different amounts of total phenolic, total flavonoid and three major flavones; baicalin, baicalein and chrysin contents. Young fruit extract, which contained low amounts of flavone contents, still promoted antibacterial effects against the tested bacteria with IC50 values lower than 1 mg/mL and MIC values between 4 to 10 mg/mL in S. intermedius, S. aureus and S suis while higher IC50 and MIC values against P. aeruginosa and β-hemolytic E. coli were found. From scanning electron microscopy, the extract of the young fruit of O. indicum promoted morphological changes in the bacterial cells by disrupting the bacterial cell walls, inducing leakage of the cellular content, and generating the abnormal accumulation of cells. The mechanism of action of the extract for this antibacterial effect may be the disruption of the cell membrane and abnormal cell aggregations. Regression analysis of the results suggests the correlation between total phenolic and total flavonoid contents and antioxidant and antibacterial effects. Baicalin was found to have a high correlation with an inhibitory effect against β-hemolytic E. coli while three unidentified peaks, which could be flavones, showed high correlations with an inhibitory effect against S. intermedius, S. suis, P. aeruginosa and S. aureus.

scholarly journals Synthesis and Characterization of Polyvinylpyrrolidone-Modified ZnO Quantum Dots and Their In Vitro Photodynamic Tumor Suppressive Action

2021 ◽  
Vol 22 (15) ◽  
pp. 8106
Author(s):  
Tianming Song ◽  
Yawei Qu ◽  
Zhe Ren ◽  
Shuang Yu ◽  
Mingjian Sun ◽  
...  
Keyword(s):  
Quantum Dots ◽  
Photodynamic Therapy ◽  
Inhibitory Effect ◽  
Therapeutic Effects ◽  
In Vivo Experiments ◽  
Potential Applications ◽  
Zno Quantum Dots ◽  
Zno Qds

Despite the numerous available treatments for cancer, many patients succumb to side effects and reoccurrence. Zinc oxide (ZnO) quantum dots (QDs) are inexpensive inorganic nanomaterials with potential applications in photodynamic therapy. To verify the photoluminescence of ZnO QDs and determine their inhibitory effect on tumors, we synthesized and characterized ZnO QDs modified with polyvinylpyrrolidone. The photoluminescent properties and reactive oxygen species levels of these ZnO/PVP QDs were also measured. Finally, in vitro and in vivo experiments were performed to test their photodynamic therapeutic effects in SW480 cancer cells and female nude mice. Our results indicate that the ZnO QDs had good photoluminescence and exerted an obvious inhibitory effect on SW480 tumor cells. These findings illustrate the potential applications of ZnO QDs in the fields of photoluminescence and photodynamic therapy.

scholarly journals Synthesis of Some Polysubstituted Nicotinonitriles and Derived Pyrido[2,3-d]pyrimidines asIn VitroCytotoxic and Antimicrobial Candidates

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Hassan M. Faidallah ◽  
Sherif A. F. Rostom ◽  
Khalid A. Khan
Keyword(s):  
Cell Line ◽  
Colon Carcinoma ◽  
Human Tumor ◽  
Human Colon ◽  
Pyrimidine Ring ◽  
Inhibitory Effect ◽  
Breast Adenocarcinoma ◽  
Human Tumor Cell Lines ◽  
E Coli

The synthesis of polysubstituted pyridines, in addition to some derived pyrido[2,3-d]pyrimidine ring systems supported with chemotherapeutically active functionalities, is described. They were evaluated for theirin vitrocytotoxic effects against three different human tumor cell lines (human colon carcinoma HT29, hepatocellular carcinoma Hep-G2, and Caucasian breast adenocarcinoma MCF7). Nine compounds displayed variable cytotoxic potential, among which alkylthio analogs33,34, and37emerged as the most active members, being almost twice as active as doxorubicin against the colon carcinoma HT29 cell line. In addition, the same three analogs showed a clear differential cytotoxic profile as they exhibited a marginal inhibitory effect on the growth of the normal nontransformed human foreskin fibroblast Hs27 cell line. Meanwhile, nineteen compounds were able to exhibit significant antibacterial activity against both Gram-positive and Gram-negative bacteria, together with moderate antifungal activities. The pyrido[2,3-d]pyrimidine-2(1H)-thione30together with its alkylthio derivatives33and34stemmed as the most active antimicrobial members being equipotent to ampicillin againstS. aureus,E. coli,andP. aeruginosa,together with a noticeable antifungal activity againstC. albicans.Compounds33and34could be considered as a promising template for possible dual antimicrobial-anticancer candidates.

scholarly journals Photothermal-assisted antibacterial application of GO-Ag against clinical isolated MDR E. coli

2019 ◽  
Author(s):  
Yuqing Chen ◽  
Wei Wu ◽  
Zeqiao Xu ◽  
Cheng Jiang ◽  
Shuang Han ◽  
...  
Keyword(s):  
Graphene Oxide ◽  
Near Infrared ◽  
Antibacterial Effect ◽  
Luria Bertani ◽  
Fluorescent Imaging ◽  
Photothermal Effect ◽  
Antibacterial Efficiency ◽  
E Coli ◽  
Morphology Characterization

Abstract Background: Treatment of multidrug-resistant (MDR) bacterial infection is a great challenge in public health. Herein, we provide a solution to this problem with the use of graphene oxide-silver (GO-Ag) nanocomposites as anti-bacterial agent. Methods: Following established protocols, silver nanoparticles were grown on graphene oxide sheets. Then, a series of in-vitro studies were conducted to validate the antibacterial efficiency of the GO-Ag nanocomposites against clinical MDR Escherichia coli (E. coli) strains. Firstly, minimum inhibitory concentrations (MICs) of different antimicrobials were tested against MDR E. Coli strains. Then, bacteria viability assessments were conducted with different nanomaterials in Luria-Bertani (LB) broth. Afterwards, photothermal irradiation was conducted on MDR E. coli with lower GO-Ag concentration. At last, fluorescent imaging and morphology characterization using scanning electron microscope (SEM) were done to find the possible cause of antibacterial effect. Results: GO-Ag nanocomposites showed the highest antibacterial efficiency among tested antimicrobials. Synergetic antibacterial effect was observed in GO-Ag nanocomposites treated group. The remained bacteria viabilities were 4.4% and 4.1% respectively for different bacteria strains with GO-Ag concentration at 14.0 µg mL-1. In addition, GO-Ag nanocomposites have strong absorption in the near-infrared field and can convert the electromagnetic energy to heat. With the use of this photothermal effect, effective sterilization could be achieved using GO-Ag nanocomposites concentration as low as 7.0 µg mL-1. Fluorescent imaging and morphology characterization were used to analyze bacteria living status, which uncovered that bacteria integrity was disrupted after GO-Ag nanocomposites treatment. Conclusions: GO-Ag nanocomposites are proved to be efficient antibacterial agent against multi-drug resistant E. coli. Their strong antibacterial effect arises from inherent antibacterial property and photothermal effect that provides aid for bacteria killing.

scholarly journals Degradation of Myogenic Transcription Factor MyoD by the Ubiquitin Pathway In Vivo and In Vitro: Regulation by Specific DNA Binding

1998 ◽  
Vol 18 (10) ◽  
pp. 5670-5677 ◽  
Author(s):  
Ossama Abu Hatoum ◽  
Shlomit Gross-Mesilaty ◽  
Kristin Breitschopf ◽  
Aviad Hoffman ◽  
Hedva Gonen ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
Specific Inhibitor ◽  
Inhibitory Effect ◽  
26S Proteasome ◽  
Intact Cells ◽  
Free System ◽  
Ubiquitin System

ABSTRACT MyoD is a tissue-specific transcriptional activator that acts as a master switch for skeletal muscle differentiation. Its activity is induced during the transition from proliferating, nondifferentiated myoblasts to resting, well-differentiated myotubes. Like many other transcriptional regulators, it is a short-lived protein; however, the targeting proteolytic pathway and the underlying regulatory mechanisms involved in the process have remained obscure. It has recently been shown that many short-lived regulatory proteins are degraded by the ubiquitin system. Degradation of a protein by the ubiquitin system proceeds via two distinct and successive steps, conjugation of multiple molecules of ubiquitin to the target protein and degradation of the tagged substrate by the 26S proteasome. Here we show that MyoD is degraded by the ubiquitin system both in vivo and in vitro. In intact cells, the degradation is inhibited by lactacystin, a specific inhibitor of the 26S proteasome. Inhibition is accompanied by accumulation of high-molecular-mass MyoD-ubiquitin conjugates. In a cell-free system, the proteolytic process requires both ATP and ubiquitin and, like the in vivo process, is preceded by formation of ubiquitin conjugates of the transcription factor. Interestingly, the process is inhibited by the specific DNA sequence to which MyoD binds: conjugation and degradation of a MyoD mutant protein which lacks the DNA-binding domain are not inhibited. The inhibitory effect of the DNA requires the formation of a complex between the DNA and the MyoD protein. Id1, which inhibits the binding of MyoD complexes to DNA, abrogates the effect of DNA on stabilization of the protein.

scholarly journals In Vivo Modulation of a DnaJ Homolog, CbpA, by CbpM

2007 ◽  
Vol 189 (9) ◽  
pp. 3635-3638 ◽  
Author(s):  
Matthew R. Chenoweth ◽  
Nancy Trun ◽  
Sue Wickner
Keyword(s):  
Escherichia Coli ◽  
Cell Growth ◽  
Stationary Phase ◽  
Specific Inhibitor ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
E Coli ◽  
Hsp70 Chaperone

ABSTRACT CbpA, an Escherichia coli DnaJ homolog, can function as a cochaperone for the DnaK/Hsp70 chaperone system, and its in vitro activity can be modulated by CbpM. We discovered that CbpM specifically inhibits the in vivo activity of CbpA, preventing it from functioning in cell growth and division. Furthermore, we have shown that CbpM interacts with CbpA in vivo during stationary phase, suggesting that the inhibition of activity is a result of the interaction. These results reveal that the activity of the E. coli DnaK system can be regulated in vivo by a specific inhibitor.

scholarly journals The protective role of microRNA-21 against coxsackievirus B3 infection through targeting the MAP2K3/P38 MAPK signaling pathway

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Feng He ◽  
Zonghui Xiao ◽  
Hailan Yao ◽  
Sen Li ◽  
Miao Feng ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Cell Apoptosis ◽  
Specific Inhibitor ◽  
Inhibitory Effect ◽  
Mapk Signaling ◽  
Apoptosis Rate ◽  
Cvb3 Infection ◽  
Interfering Rna

Abstract Background The P38 mitogen-activated protein kinase (MAPK) pathway plays an essential role in CVB3-induced diseases. We previously demonstrated microRNA-21 has potential inhibitory effect on the MAP2K3 which locates upstream of P38 MAPK and was upregulated in mouse hearts upon CVB3 infection. However, the effect and underlying mechanism of miRNA-21 on CVB3 infection remain unclear. Methods We detected continuous changes of cellular miRNA-21 and P38 MAPK proteins expression profiling post CVB3 infection in vitro within 12 h. P38 MAPK signaling was inhibited by the specific inhibitor, small interfering RNA and miRNA-21 mimic in vitro, CVB3 replication, cell apoptosis rate and proliferation were detected. Viral load in the mice heart, cardiomyocyte apoptosis rate and histological of the heart were also detected in the mice model of viral myocarditis pretreated with miRNA-21-lentivirus. Results We observed significant upregulation of miRNA-21 expression followed by suppression of the MAP2K3/P38 MAPK signaling in CVB3-infected Hela cells. The inactivation of the MAP2K3/P38 MAPK signaling by P38 MAPK specific inhibitor, small interfering RNA against MAP2K3, or miRNA-21 overexpression significantly inhibited viral progeny release from CVB3-infected cells. Mechanistically, when compared with control miRNA, miRNA-21 showed no effect on capsid protein VP1 expression and viral load within host cells, while significantly reversing CVB3-induced caspase-3 activation and cell apoptosis rate, further promoting proliferation of infected cells, which indicates the inhibitory effect of miRNA-21 on CVB3 progeny release. In the in vivo study, when compared with control miRNA, miRNA-21 pretreatment remarkably inactivated the MAP2K3/P38 MAPK signaling in mice and protected them against CVB3 infection as evidenced by significantly alleviated cell apoptosis rate, reduced viral titers, necrosis in the heart as well as by remarkably prolonged survival time. Conclusions miRNA-21 were reverse correlated with P38 MAPK activation post CVB3 infection, miRNA-21 overexpression significantly inhibited viral progeny release and decreased myocytes apoptosis rate in vitro and in vivo, suggesting that miRNA-21 may serve as a potential therapeutic agent against CVB3 infection through targeting the MAP2K3/P38 MAPK signaling.

scholarly journals Chitosan-based nanoparticles sustenance and potentiation of the antibacterial effect of ampicillin against drug resistance among strains of Escherichia coli

Bio-Research ◽  
2020 ◽  
Vol 18 (2) ◽  
Author(s):  
EB Onuigbo ◽  
C Anozie-Ikeanyi ◽  
NE Edeh ◽  
CO Eze ◽  
TH Gugu
Keyword(s):  
Drug Resistance ◽  
Drug Release ◽  
Encapsulation Efficiency ◽  
Antibacterial Effect ◽  
Sodium Tripolyphosphate ◽  
Chitosan Nanoparticles ◽  
In Vitro Drug Release ◽  
E Coli ◽  
Ampicillin Trihydrate

The study seeks to evaluate nanoparticles based on chitosan for enhanced delivery of ampicillin in plasmid-mediated drug resistance. Serial dilutions of a mixed population of E. coli was plated on nutrient agar and streaked on Replica-plate 25 random colonies using MacConkey agar with or without ampicillin (100 µg/ml) daily for 96 h. Nanoparticles were prepared by cross-linking chitosan with sodium tripolyphosphate with ampicillin trihydrate adsorbed. Three different batches were prepared for optimization. The nanoparticles were optimized based on encapsulation efficiency, in vitro drug release, pH stability and microbiological assay using two laboratory strains of E. coli. Increased resistance to ampicillin due to possible plasmid transfer was established in vitro after 96 h. The encapsulation efficiency of the three batches was between 21-57 %. The drug release showed a burst effect and slow extended release over 8 h and reached a peak of about 19 % release at the 6 and 7 h in Batch A, B and C. The pH of the particles was stable over a period of 6 d. The nanoparticles containing only 0.075 mg of ampicillin dropped in an agar well plate inoculated with 1 ml of E. coli J62 lac pro trp hispFlac::Tn3 (AmpR) gave an IZD of ≥ 25 mm. Chitosan nanoparticles holds good potentials in potentiating the antibacterial effect of ampicillin against possible plasmid-mediated drug resistance

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