Bacterial Growth Kinetics of &lt;i&gt;E. coli&lt;/i&gt; in the Presence of Various Trimethoprim Derivatives Alone and in Combination with Sulfonamides

Seydel, Joachim K.; Wempe, E

doi:10.1159/000237928

Cited by 10 publications

(9 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This general hypothesis is consistent with the results of the SPE-MS time course, although the assays were carried out under different inoculum conditions and so cannot be directly compared. Other metabolic targets, such as folate inhibitors, exhibit a similar lag in growth inhibition when tested in time-kill studies . Further study may describe in greater detail how CoA biosynthesis inhibition leads to cell death.…”

Section: Resultsmentioning

confidence: 97%

Optimization of CoaD Inhibitors against Gram-Negative Organisms through Targeted Metabolomics

et al. 2017

View full text Add to dashboard Cite

Drug-resistant Gram-negative bacteria are of increasing concern worldwide. Novel antibiotics are needed, but their development is complicated by the requirement to simultaneously optimize molecules for target affinity and cellular potency, which can result in divergent structure-activity relationships (SARs). These challenges were exemplified during our attempts to optimize inhibitors of the bacterial enzyme CoaD originally identified through a biochemical screen. To facilitate lead optimization, we developed mass spectroscopy assays based on the hypothesis that levels of CoA metabolites would reflect the cellular enzymatic activity of CoaD. Using these methods, we were able to monitor the effects of cellular enzyme inhibition at compound concentrations up to 100-fold below the minimum inhibitory concentration (MIC), a common metric of growth inhibition. Furthermore, we generated a panel of efflux pump mutants to dissect the susceptibility of a representative CoaD inhibitor to efflux. These approaches allowed for a nuanced understanding of the permeability and efflux liabilities of the series and helped guide optimization efforts to achieve measurable MICs against wild-type E. coli.

show abstract

Section: Resultsmentioning

confidence: 97%

Optimization of CoaD Inhibitors against Gram-Negative Organisms through Targeted Metabolomics

et al. 2017

View full text Add to dashboard Cite

show abstract

“…In the cases of SA and sulfones, we were able to demonstrate that such an analog of 7,8-dihydropteroic acid is indeed produced [9,26] in E. coli. If the k5o values are used in the regression analysis for the highly active SA instead of the i50 values, the correlation between the logarithm of the biological activity and the physicochemical parameters becomes more significant [Eq.…”

Section: Kinetics Of Inhibition In a Cell-free Systemmentioning

confidence: 97%

Mode of action and quantitative structure–activity relationship of sulfonamides in biological systems of different complexity (enzymes, bacteria, rat, and human)

Seydel

1981

Int J of Quantum Chemistry

View full text Add to dashboard Cite

The mode of action of sulfonamides is evaluated and described and the structural dependency of the inhibitory effect of sulfonamides against isolated enzymes as well as against whole cell bacteria is quantitatively described as a function of the variation of electronic and steric influences of the various substituents. In addition the structural dependence of various pharmacokinetic properties as rate of absorption, distribution, metabolism, and excretion on structural changes in the sulfonamide molecules is quantitatively derived. In contrast to the preconditions for inhibitory activity, changes in lipophilicity play the dominant role in pharmacokinetics of sulfonamides.

show abstract

“…Many studies have examined the resistance of enteric bacteria in humans after antibiotic therapy [4][5][6][7][8], but there is much less information available on the prevalence of antibiotic resistance in the faecal flora of healthy adults who have not used antibiotics recently [9][10][11][12][13]. However, such subjects are potential recipients of antimicrobial agents.…”

Section: Introductionmentioning

confidence: 99%

Resistance in faecal Escherichia coli isolated from pigfarmers and abattoir workers

Nijsten¹,

London²,

Bogaard³

et al. 1994

Epidemiol. Infect.

View full text Add to dashboard Cite

Faecal samples collected from three populations of healthy adult volunteers (290 pigfarmers, 316 abattoir workers, 160 (sub)urban residents) living in the south of The Netherlands were analysed for the prevalence and degree of antibiotic resistance of Escherichia coli. Significant differences in prevalence of resistance to amoxicillin, neomycin, oxytetracycline, sulfamethoxazole and trimethoprim were observed. The pigfarmers showed the highest percentages of resistance and the (sub)urban residents the lowest. In contrast no significant differences in high degrees of resistance were observed, except for neomycin. Although both pigfarmers and abattoir workers have regular contact with pigs differences in prevalences of resistance were observed. However, because abattoir workers with intensive and less intensive pig(carcass) contact did not show significant differences, this is probably not the only important source of resistant E. coli in pigfarmers. The high antibiotic use by pigfarmers (5%) and abattoir workers (8%) than by (sub)urban residents (0%) did not result in significantly different resistance percentages.

show abstract

Bacterial Growth Kinetics of <i>E. coli</i> in the Presence of Various Trimethoprim Derivatives Alone and in Combination with Sulfonamides

Cited by 10 publications

References 4 publications

Optimization of CoaD Inhibitors against Gram-Negative Organisms through Targeted Metabolomics

Optimization of CoaD Inhibitors against Gram-Negative Organisms through Targeted Metabolomics

Mode of action and quantitative structure–activity relationship of sulfonamides in biological systems of different complexity (enzymes, bacteria, rat, and human)

Resistance in faecal Escherichia coli isolated from pigfarmers and abattoir workers

Contact Info

Product

Resources

About