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Publication: Vandal OH, Roberts JA, Odaira T, Schnappinger D, Nathan CF, Ehrt S. Acid-susceptible mutants of Mycobacterium tuberculosis share hypersusceptibility to cell wall and oxidative stress and to the host environment. J Bacteriol. 2009 Jan;191(2):625-31. doi: 1. 11/2008. Tags: Drug Discovery, Drug Targets, M.tb. Biology ...
This study was done to look at the effect of a variety of antimicrobial agents on several microorganisms. This response is usually determined by the agents mode of action and the structure of the microbe. The experiment involved applying antimicrobial disks onto agar inoculated with the test microbe. Zones of inhibition were measured after 18 hours to determine each reaction as sensitive, resistant, or intermediate. Staph. Aureus, a gram positive organism with a thick cell wall, was very sensitive to all agents except Nalidixic acid. P. Aeruginosa showed resistance to all but Streptomycin which had an intermediate effect. E. coli was resistant to all but Chloramphenicol and Nalidixic acid. These results were consistent with the fact that E. coli and P. Aeruginosa are gram negative organisms which exhibit a thin cell wall of peptidoglycan with an outer membrane acting as a barrier against some antibiotics. Further experiments should investigate the sensitivity or resistance of strains from ...
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Birth of fluroquinolones as a class of antibiotics dates back to the discovery of nalidixic acid in th early 1960s. Mechanism of Action Fluroquinolones inhibits DNA Gyrase enzyme which is essential for DNA replication, thereby inhibits DNA Synthesis.It als
We considered a prediction confirmed only if: (1) the survival of a mutant was ,25% of the wild-type, when grown with the antibiotic inhibiting the process GORBI has predicted, and (2) the survival of the mutant was ,50% of the wild-type when grown on the other two antibiotics, here used as negative controls.. For example, we predicted DNA damage response for the E. coli yfgI gene: when grown with DNA-damaging nalidixic acid, the yfgI mutant had 7% survival of the wild type, but when grown on kasugamycine or ampicilin, the survival was much higher: 98% and 74% of the wild type, respectively. We therefore consider this prediction confirmed: the yfgI mutant is sensitive to a DNA-damaging agent, while exhibiting wild type-like resistance to other stresses.. With these criteria, 25 out of 38 genes had confirmed predictions, equivalent to an experimental Precision of 66% (95% C.I. 51%-81%). This agrees well with the expected Precision of ≥60%, show that our estimates of accuracy are ...
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Although not formally a quinolone, nalidixic acid is considered the first quinolone drug. It was introduced in 1962 for treatment of urinary tract infections in humans.[70] Nalidixic acid was discovered by George Lesher and coworkers in a distillate during an attempt at chloroquine synthesis.[71] Nalidixic acid is thus considered to be the predecessor of all members of the quinolone family, including the second, third and fourth generations commonly known as fluoroquinolones. Since the introduction of nalidixic acid in 1962, more than 10,000 analogs have been synthesized, but only a handful have found their way into clinical practice. The first generation also included other quinolone drugs, such as pipemidic acid, oxolinic acid, and cinoxacin, which were introduced in the 1970s. They proved to be only marginal improvements over nalidixic acid.[72] These drugs were widely used as a first line treatment for many infections, including very commons ones like acute sinusitis, acute bronchitis, and ...
Sandwiches, prepared with home-cooked or commercially purchased turkey meat and made with or without commercially available mayonnaise, were inoculated with approximately 600-700 cells of a nalidixic acid-resistant strain of Salmonella typhimurium per gram of each sandwich. The sandwiches were incubated at 4, 21, and 30 C and samples analyzed at 4, 8 and 24 h for the number of S. typhimurium cells. Significant increases in the number of S. typhimurium cells were found in sandwiches prepared without mayonnaise and containing home cooked turkey meat after 8 h of incubation at 30 C and 24 h of incubation at 21 or 30 C. The increase in numbers of S. typhimurium in sandwiches prepared with commercially processed turkey meat was significantly lower than the increase in sandwiches prepared with home-cooked turkey meat. Mayonnaise had a significant inhibitory effect on growth of S. typhimurium in sandwiches prepared with turkey breast meat; however, mayonnaise did not prevent Salmonella from multiplying ...
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When DNA gyrase is trapped on bacterial chromosomes by quinolone antibacterials, reversible complexes form that contain DNA ends constrained by protein. Two subsequent processes lead to rapid cell death. One requires ongoing protein synthesis; the other does not. The prototype quinolone, nalidixic acid, kills wild-type Escherichia coli only by the first pathway; fluoroquinolones kill by both. Both lethal processes correlated with irreversible chromosome fragmentation, detected by sedimentation and viscosity of DNA from quinolone-treated cells. However, only fluoroquinolones fragmented purified nucleoids when incubated with gyrase purified from wild-type cells. A GyrA amino acid substitution (A67S) expected to perturb a GyrA-GyrA dimer interface allowed nalidixic acid to fragment chromosomes and kill cells in the absence of protein synthesis; moreover, it made a non-inducible lexA mutant hypersusceptible to nalidixic acid, a property restricted to fluoroquinolones with wild-type cells. The GyrA variation
Using flow cytometry, we previously established in an ex vivo model that fluoroquinolones induce a stimulation of the oxidative metabolism in immature chondrocytes. To assess these findings in an in vitro model, primary cultures of immature articular chondrocytes were incubated with four quinolone solutions: ofloxacin, ciprofloxacin, nalidixic acid at 10 micrograms/ml for 24 hr and pefloxacin at 1, 10 and 100 micrograms/ml for various periods of time (2, 4, 6, 12, 24 and 48 hr). Three fluorochromes were used: DCFH-DA, reflecting cellular production of H2O2, rhodamine 123 (Rh123) and 10-N-nonyl-acridine orange (NAO), which are specific for mitochondrial activity and mass, respectively. In immature chondrocyte cultures treated with pefloxacin, ofloxacin and nalidixic acid at 10 micrograms/ml for 24 hr, levels of cellular fluorescent dichlorofluorescein DCF (oxidized form of DCFH-DA) were significantly higher than in control cells. No significant increase could be registered with ciprofloxacin. In ...
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Quino-what?. We hear that a lot.. Before we explain what it is and why we are committed to helping victims, lets start with how it is pronounced.. Quinolone: kwĭnə-lōn. Fluoroquinolone: flu̇r-ō-ˈkwi-nə-ˌlōn\ History and difference between quinolones and fluoroquinolones.. The words quinolone and fluoroquinolone are often interchanged but there is a difference between the two. Both are terms for a class of antibiotics based on Nalidixic acid.. Nalidixic acid is the first of the synthetic quinolone antibiotics. It was discovered in 1962 by George Lesher and used clinically in 1967. Originally, in smaller doses Nalidixic acid inhibited growth and replication of bacteria; in higher doses it killed bacteria.. The addition of a fluorine atom is what differentiates quinolones from fluoroquinolones. Fluorine is an element; F2 on the Periodic Table. It is a toxic gas and is considered one of the most reactive elements. The addition of the fluorine atom and a piperazine ring make ...
The accumulation of nalidixic acid and 14 fluoroquinolones over a range of external drug concentrations (10-100 mg/L; c. 25-231 microM) into intact cells of Escherichia coli KL-16, Staphylococcus aureus NCTC 8532, Pseudomonas aeruginosa NCTC 10662 and spheroplasts of E. coli was investigated. The effect of 100 microM carbonyl cyanide m-chlorophenyl hydrazone (CCCP) upon the concentration of quinolone accumulated by intact cells and spheroplasts of E. coli was also determined. Except for pefloxacin, there was an increase in the concentration of the six quinolones examined accumulated by E. coli, despite a reduction in fluorescence at alkaline pH. For ciprofloxacin the partition coefficient (P(app)) was constant despite an increase in the pH; however, the P(app) for nalidixic acid decreased significantly with an increase in pH. The concentration of nalidixic acid, ciprofloxacin and enrofloxacin accumulated by E. coli and S. aureus increased with an increase in temperature up to 40 degrees C and 50 ...
Nalidixic acid resistance among Salmonella Typhimurium clinical isolates has steadily increased, whereas the level of ciprofloxacin resistance remains low. The main objective of this study was to characterize the fluoroquinolone resistance mechanisms acquired in a S. Typhimurium mutant selected with ciprofloxacin from a susceptible isolate and to investigate its invasion ability ...
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0035] First, suitable cell enlargers according to the best mode are not particularly limited, as long as (1) at predetermined concentrations, they are disposed to inhibit or suppress cell division to allow microbial cells to enlarge, and (2) when the concentrations are lowered, they will be disposed to lose the action of inhibiting or suppressing cell division, exerting no adverse effect on normal proliferation and other functions (reversible), example of which may include cell division inhibitors for terminating cell division, for example, agents having inhibitory action on enzymes involved in cell division (such as antibiotics and agricultural chemicals). Specific examples of agents having such properties may include pyridonecarboxylic acid-based antibiotics (for example, nalidixic acid, pipemidic acid and piromidic acid). When the cell enlargers are used, cells grow to lengths or sizes approximately three to four times as large as the normal sizes, for example. Here, different types of cell ...
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We compared various spectroscopic properties of a norfloxacin-single stranded DNA complex with those of norfloxacin-double stranded DNA complex. Norfloxacin binds to both double- and single stranded DNA, and we observed the following spectroscopic changes for both complexes: hypochromism in the norfloxacin absorption region in the absorption spectrum, the characteristic induced CD spectrum consisting of a weak positive band at 323 nm and a strong positive band at 280-300 nm followed by a negative band in the 260 nm region, a strong decrease in the fluorescence intensity and a red-shift in the fluorescence emission spectrum, and shorter fluorescence decay times. These results indicate that the environments of the bound norfloxacin in both DNAs are similar, although the equilibrium constant of the norfloxacin-single stranded DNA was twice as high as the norfloxacin-double stranded DNA complex. Both complexes were thermodynamically favored with similar negative ΔGo. Negative ΔHo terms contribute ...
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