1,724,424 research outputs found
WQ-3810 exerts high inhibitory effect on quinolone-resistant DNA gyrase of Salmonella Typhimurium
Full text linkThe inhibitory effect of WQ-3810 on DNA gyrase was assayed to evaluate the potential of WQ-3810 as a candidate drug for the treatment of quinolone resistant Salmonella Typhymurium infection. The inhibitory effect of WQ-3810, ciprofloxacin and nalidixic acid was compared by accessing the drug concentration that halves the enzyme activity (IC50) of purified S. Typhimurium wildtype and mutant DNA gyrase with amino acid substitution at position 83 or/and 87 in subunit A (GyrA) causing quinolone resistance. As a result, WQ-3810 reduced the enzyme activity of both wildtype and mutant DNA gyrase at a lower concentration than ciprofloxacin and nalidixic acid. Remarkably, WQ-3810 showed a higher inhibitory effect on DNA gyrase with amino acid substitutions at position 87 than with that at position 83 in GyrA. This study revealed that WQ-3810 could be an effective therapeutic agent, especially against quinolone resistant Salmonella enterica having amino acid substitution at position 87. (Up to 150 words
WQ-3810: A new fluoroquinolone with a high potential against fluoroquinolone-resistant Mycobacterium tuberculosis
Full text linkFluoroquinolone (FQ) resistance in Mycobacterium tuberculosis (Mtb), caused by amino acid substitutions in DNA gyrase, has been increasingly reported worldwide. WQ-3810 is a newly developed FQ that is highly active against FQ-resistant pathogens; however, its activity against Mtb has not been evaluated. Herein we examined the efficacy of WQ-3810 against Mtb through the use of recombinant Mtb DNA gyrases. In addition, in vitro anti-mycobacterial activity of WQ-3810 was evaluated against recombinant Mtb var. bovis Bacille Calmette-Guerin strains in which gyrase-coding genes were replaced with Mtb variants containing resistance-conferring mutations. WQ-3810 showed a higher inhibitory activity than levofloxacin against most recombinant DNA gyrases with FQ-resistance mutations. Furthermore, WQ-3810 showed inhibition even against a DNA gyrase variant harboring a G88C mutation which is thought to confer the highest resistance against FQs in clinical Mtb isolates. In contrast, the FQ susceptibility test showed that WQ-3810 had relatively weak mycobactericidal activity compared with moxifloxacin. However, the combination of WQ-3810 and ethambutol showed the greatest degree of synergistic activity against recombinant strains. Since FQs and ethambutol have been used in multi-drug therapy for tuberculosis, WQ-3810 might represent a new, potent anti-tuberculosis drug that can be effective even against FQ-resistant Mtb strains
WQ-3810 inhibits DNA gyrase activity in ofloxacin-resistant Mycobacterium leprae
Full text linkBackground: Mycobacterium leprae causes leprosy and ofloxacin is used to control this bacterium. However, specific amino acid substitutions in DNA gyrases of M. leprae interferes with the effect of ofloxacin. Methodology/principal findings: Here we tested the inhibitory effect of WQ-3810 on DNA gyrases in M. leprae, using recombinant gyrases. We theorized that WQ-3810 and DNA gyrases interacted, which was tested in silico. Compared with control drugs like ofloxacin, WQ-3810 showed a better inhibitory effect on ofloxacin-resistant DNA gyrases. The in-silico study showed that, unlike control drugs, a specific linkage between a R1 group in WQ-3810 and aspartic acid at position 464 in the subunit B of DNA gyrases existed, which would enhance the inhibitory effect of WQ-3810. This linkage was confirmed in a further experiment, using recombinant DNA gyrases with amino acid substitutions in subunits B instead. Conclusions/significance: The inhibitory effect of WQ-3810 was likely enhanced by the specific linkage between a R1 group residue in its structure and DNA gyrases. Using interactions like the one found in the present work may help design new fluoroquinolones that contribute to halt the emergence of antibiotic-resistant pathogens. (c) 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved
Southern Pacific (SP) 3810
No full textA photograph postcard showing the Southern Pacific (SP) 3810, 2-8-8-4, Tucumcari, NM
Santa Fe (ATSF) 3810
No full textA photograph postcard showing the Santa Fe (ATSF) 3810, 2-8-8-4, passing Hargis, NM, at dusk, westbound from Tucumcari with 70 cars
Block Card 3810 Schneider Road
No full textThis image was produced by the Auditor's Office in Lucas County, Ohio for tax assessment purposes. Associated dates are approximate. Descriptive terms related to this photograph include: Garrison Colonial Style | 3810 Schneider Road (Toledo, Ohio) | Dwelling | Crossgates Plat (Toledo, Ohio) | South Toledo Area (Toledo, Ohio
Block Card 3810 Angola Road
No full textThis image was produced by the Auditor's Office in Lucas County, Ohio for tax assessment purposes. Associated dates are approximate. Descriptive terms related to this photograph include: 3810 Angola Road (Toledo, Ohio) | Dwelling | Adams Township Area (Toledo, Ohio) | Folk House Style | Gable front house
Технологические решения для строительства разведочной вертикальной скважины глубиной 3810 метров на газоконденсатном месторождении(Тюменская область)
Full text linkОбъектом ВКР служит разведочная вертикальная скважина глубиной 3810 метров на газоконденсатном месторождении (Тюменская область). Целью данной работы является – спроектировать технологическое решения для бурения вертикальной разведочной скважины глубиной 3810 метров на газоконденсатном месторождении (Тюменская область).The object of the WRC is an exploratory vertical well with a depth of 3810 meters at a gas condensate field (Tyumen region). The purpose of this work is to design a technological solution for drilling a vertical exploration well with a depth of 3810 meters at a gas condensate field (Tyumen region)
Block Card 3810 S. Beverly Hills Drive
No full textThis image was produced by the Auditor's Office in Lucas County, Ohio for tax assessment purposes. Associated dates are approximate. Descriptive terms related to this photograph include: 3810 South Beverly Hills Drive (Toledo, Ohio) | Albert J. Coreys Beverly Hills (Toledo, Ohio) | South Toledo Area (Toledo, Ohio) | Ranch houses | Dwellin
WQ-3810, a fluoroquinolone with difluoropyridine derivative as the R1 group exerts high potency against quinolone-resistant Campylobacter jejuni
No full textABSTRACT Quinolone-resistant Campylobacter jejuni have been increasing worldwide. Quinolones exert their antibacterial activity by inhibiting DNA gyrase, but most of the isolates acquire quinolone resistance via an amino acid substitution in the A subunit of DNA gyrase. WQ-3810 is a quinolone antibiotic that has been reported to have high potency even to DNA gyrase with amino acid substitutions in several bacterial species; however, there was no information on C. jejuni. Hence, this study aimed to evaluate the activity of WQ-3810 to inhibit wild-type/mutant DNA gyrases of C. jejuni and the bacterial growth for accessing the potency for the treatment of quinolone-resistant C. jejuni infection. The inhibitory activity of WQ-3810 was assessed and compared with ciprofloxacin and nalidixic acid by calculating the half maximal inhibitory concentration (IC50) against wild-type/mutant DNA gyrases. Next, the minimum inhibitory concentration (MIC) of WQ-3810 and five other quinolones was determined for C. jejuni including quinolone-resistant strains with amino acid substitutions in GyrA. Furthermore, the interaction between WQ-3810 and wild-type/mutant DNA gyrase was speculated using docking simulations. The IC50 of WQ-3810 against wild-type DNA gyrase was 1.03 µg/mL and not different from that of ciprofloxacin. However, those of WQ-3810 against mutant DNA gyrases were much lower than ciprofloxacin. The MICs of WQ-3810 ranged <0.016–0.031 µg/mL and were the lowest against both quinolone-susceptible and quinolone-resistant strains among the examined quinolones. The results obtained by the docking simulation agreed well with this observation. WQ-3810 seems to be a promising antimicrobial agent for the infections caused by quinolone-resistant C. jejuni.IMPORTANCEWQ-3810, a relatively new quinolone antibiotic, demonstrates exceptional antibacterial properties against certain pathogens in previous studies. However, its efficacy against quinolone-resistant Campylobacter jejuni was not previously reported. The prevalence of quinolone-resistant C. jejuni as a cause of foodborne illnesses is increasing, prompting this investigation into the effectiveness of WQ-3810 as a countermeasure. This study revealed high inhibitory activity of WQ-3810 against both wild-type and mutant DNA gyrases of C. jejuni. WQ-3810 was equally efficacious as ciprofloxacin against wild-type DNA gyrases but showed superior effectiveness against mutant DNA gyrases. WQ-3810 also demonstrated the lowest minimum inhibitory concentrations, highlighting its enhanced potency against both susceptible and resistant strains of C. jejuni. This observation was well supported by the results of the in silico analysis. Consequently, WQ-3810 exhibits a higher level of bactericidal activity compared to existing quinolones in combating both susceptible and resistant C. jejuni isolates
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