scholarly journals QUANTITATIVE STUDIES OF SULFONAMIDE RESISTANCE

1943 ◽  
Vol 77 (1) ◽  
pp. 29-39 ◽  
Author(s):  
William M. M. Kirby ◽  
Lowell A. Rantz

1. In vitro experiments were performed with E. coli, using a method designed for the quantitative study of various aspects of sulfonamide resistance. 2. Resistance was found to be a gradually developing process, and was demonstrated for all four drugs tested, sulfanilamide, sulfapyridine, sulfathiazole, and sulfadiazine. 3. It was shown that the degree of resistance developed was correlated with the bacteriostatic potency of the sulfonamides, and that organisms resistant to certain bacteriostatic concentrations of one sulfonamide were equally resistant to similar bacteriostatic concentrations of the other sulfonamides. 4. These observations were interpreted as indicating that the development of sulfonamide resistance represents an interaction between the organisms and the one common structural unit of all the sulfonamides, namely, the p-amino nucleus. It is also suggested that this interaction may involve the same enzyme system (or systems) as those concerned in the antagonism of the sulfonamides by para-aminobenzoic acid. 5. The relation of these findings to the broader aspects of sulfonamide resistance is discussed, and it is postulated that, despite reports to the contrary, all organisms susceptible to the bacteriostatic action of the sulfonamides are capable of becoming resistant to all of the sulfonamides.

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Kristyna Pluhackova ◽  
Andreas Horner

Abstract Background Lipid-protein interactions stabilize protein oligomers, shape their structure, and modulate their function. Whereas in vitro experiments already account for the functional importance of lipids by using natural lipid extracts, in silico methods lack behind by embedding proteins in single component lipid bilayers. However, to accurately complement in vitro experiments with molecular details at very high spatio-temporal resolution, molecular dynamics simulations have to be performed in natural(-like) lipid environments. Results To enable more accurate MD simulations, we have prepared four membrane models of E. coli polar lipid extract, a typical model organism, each at all-atom (CHARMM36) and coarse-grained (Martini3) representations. These models contain all main lipid headgroup types of the E. coli inner membrane, i.e., phosphatidylethanolamines, phosphatidylglycerols, and cardiolipins, symmetrically distributed between the membrane leaflets. The lipid tail (un)saturation and propanylation stereochemistry represent the bacterial lipid tail composition of E. coli grown at 37∘C until 3/4 of the log growth phase. The comparison of the Simple three lipid component models to the complex 14-lipid component model Avanti over a broad range of physiologically relevant temperatures revealed that the balance of lipid tail unsaturation and propanylation in different positions and inclusion of lipid tails of various length maintain realistic values for lipid mobility, membrane area compressibility, lipid ordering, lipid volume and area, and the bilayer thickness. The only Simple model that was able to satisfactory reproduce most of the structural properties of the complex Avanti model showed worse agreement of the activation energy of basal water permeation with the here performed measurements. The Martini3 models reflect extremely well both experimental and atomistic behavior of the E. coli polar lipid extract membranes. Aquaporin-1 embedded in our native(-like) membranes causes partial lipid ordering and membrane thinning in its vicinity. Moreover, aquaporin-1 attracts and temporarily binds negatively charged lipids, mainly cardiolipins, with a distinct cardiolipin binding site in the crevice at the contact site between two monomers, most probably stabilizing the tetrameric protein assembly. Conclusions The here prepared and validated membrane models of E. coli polar lipids extract revealed that lipid tail complexity, in terms of double bond and cyclopropane location and varying lipid tail length, is key to stabilize membrane properties over a broad temperature range. In addition, they build a solid basis for manifold future simulation studies on more realistic lipid membranes bridging the gap between simulations and experiments.


1974 ◽  
Vol 52 (10) ◽  
pp. 838-844 ◽  
Author(s):  
Mark Nwagwu ◽  
John Lianga

As a prelude to an analysis of the dependence of muscle protein synthesis on aminoacyl tRNA's, we have investigated the rates of seryl-tRNA formation, in vitro, by aminoacylating systems isolated from 11-, 14-, and 17-day chick embryonic muscle. The results show that the combination of 14-day tRNA and 14-day aminoacyl synthetase is the most efficient in seryl-tRNA formation. We have also studied the qualitative and quantitative changes in seryl-tRNA prepared from 11-, 14-, and 17-day embryonic chick muscle by chromatography of seryl-tRNA on benzoylated DEAE-cellulose columns. The results show that, although there are no qualitative differences in the chromatographic patterns of seryl-tRNA from the different ages, there are significant quantitative differences between the patterns for 11-day and 17-day seryl-tRNA on the one hand, and the pattern for 14-day seryl-tRNA on the other.


Pathogens ◽  
2018 ◽  
Vol 7 (3) ◽  
pp. 75 ◽  
Author(s):  
Wadha Alfouzan ◽  
Rita Dhar ◽  
David Nicolau

Limited data are available on susceptibilities of these organisms to some of the recently made accessible antimicrobial agents. The in vitro activities of newer antibiotics, such as, ceftolozane/tazobactam (C/T) and ceftazidime/avibactam (CZA) along with some “older” antibiotics, for example fosfomycin (FOS) and colistin (CL) were determined against selected strains (resistant to ≥ 3 antimicrobial agents) of Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Minimum inhibitory concentrations (MIC) were determined by Clinical and Laboratory Standards Institute microbroth dilution. 133 isolates: 46 E. coli, 39 K. pneumoniae, and 48 P. aeruginosa were tested. Results showed that E. coli isolates with MIC50/90, 0.5/1 μ g / mL for CL; 4/32 μ g / mL for FOS; 0.25/32 μ g / mL for C/T; 0.25/8 μ g / mL for CZA, exhibited susceptibility rates of 95.7%, 97.8%, 76.1%, and 89.1%, respectively. On the other hand, K. pneumoniae strains with MIC50/90, 0.5/1 μ g / mL for CL; 256/512 μ g / mL for FOS; 2/128 μ g / mL for C/T; 0.5/128 μ g / mL for CZA showed susceptibility rates of 92.3%, 7.7%, 51.3%, and 64.1%, respectively. P. aeruginosa isolates with MIC50/90, 1/1 μ g / mL for CL; 128/128 μ g / mL for C/T; 32/64 μ g / mL for CZA presented susceptibility rates of 97.9%, 33.3%, and 39.6%, respectively. Higher MICs were demonstrated against most of the antibiotics. However, CL retained efficacy at low MICs against most of the isolates tested.


2008 ◽  
Vol 190 (24) ◽  
pp. 7932-7938 ◽  
Author(s):  
Sang Jun Lee ◽  
Dale E. A. Lewis ◽  
Sankar Adhya

ABSTRACT The two optical forms of aldohexose galactose differing at the C-1 position, α-d-galactose and β-d-galactose, are widespread in nature. The two anomers also occur in di- and polysaccharides, as well as in glycoconjugates. The anomeric form of d-galactose, when present in complex carbohydrates, e.g., cell wall, glycoproteins, and glycolipids, is specific. Their interconversion occurs as monomers and is effected by the enzyme mutarotase (aldose-1-epimerase). Mutarotase and other d-galactose-metabolizing enzymes are coded by genes that constitute an operon in Escherichia coli. The operon is repressed by the repressor GalR and induced by d-galactose. Since, depending on the carbon source during growth, the cell can make only one of the two anomers of d-galactose, the cell must also convert one anomer to the other for use in specific biosynthetic pathways. Thus, it is imperative that induction of the gal operon, specifically the mutarotase, be achievable by either anomer of d-galactose. Here we report in vivo and in vitro experiments showing that both α-d-galactose and β-d-galactose are capable of inducing transcription of the gal operon with equal efficiency and kinetics. Whereas all substitutions at the C-1 position in the α configuration inactivate the induction capacity of the sugar, the effect of substitutions in the β configuration varies depending upon the nature of the substitution; methyl and phenyl derivatives induce weakly, but the glucosyl derivative does not.


Cephalalgia ◽  
1995 ◽  
Vol 15 (4) ◽  
pp. 265-271 ◽  
Author(s):  
G D'Andrea ◽  
AR Cananzi ◽  
F Perini ◽  
L Hasselmark

Platelets may be linked to migraine. On the one hand they are activated during the migraine attack and thus may participate in the pathogenesis of the disorder (the nature of this activation is still unknown). In order to understand this platelet anomaly, we discuss the data available in the literature. In particular, we review recent in vitro studies of a-granules and dense bodies secretion, and aggregation induced by collagen and PAF. On the other hand, platelets share many metabolic characteristics with serotonergic neurons and endothelial cells. Accordingly, platelets have been used to investigate the possible role of serotonin turnover and nitric oxide function in migraine. In both cases, the data obtained have shown peculiar abnormalities that may explain pathogenetic and clinical aspects of primary headache.


1986 ◽  
Vol 28 (3) ◽  
pp. 444-452 ◽  
Author(s):  
Gilles Charmet ◽  
Sylvie Bernard ◽  
Michel Bernard

A very large proportion of plants regenerated from anther culture of triticale F1 hybrids do not show the euploid number of chromosomes. Of 408 androgenetic plants checked for their chromosome numbers, 228 were aneuploid, of which 39 had one or several telosomes. Two observations suggest that most of the chromosome variations observed probably preexist in microspores of the F1 hybrids and would be caused by meiotic irregularities: on the one hand, the majority of these phenomena involve R-genome chromosomes, which also give rise to meiotic univalents; on the other hand, the chromosome number frequency distribution of the microspores from a fairly asyndetic hybrid fits well with that of the androgenetic plants. Thus aneuploidy and chromosome rearrangement do not implicate the in vitro technique itself but rather the choice of the material in triticale.Key words: × triticosecale, in vitro culture, chromosome variation, aneuploidy, C-banding.


1995 ◽  
Vol 14 (8) ◽  
pp. 672-678 ◽  
Author(s):  
S. Lautraite ◽  
D. Parent-Massin ◽  
B. Rio ◽  
H. Hoellinger

T-2 toxin is a trichothecene mycotoxin produced by vari ous species of fungi. Trichothecenes are known as major contaminants of cereals and their derivatives. In man as well as in animals, T-2 toxin has been shown to induce ali mentary intoxication and, among others, haematological symptoms. Granulo-monocytic progenitors from human umbilical cord blood on the one hand and granulo-mono cytic progenitors from rat bone marrow on the other, were cultured in the presence of T-2 toxin (from 10-7 to 10-10 M) for 14 days. A study of concentration and effect relation ships showed a strong and rapid effect of T-2 toxin on rat colony forming unit-granulocyte and macrophage (CFU-GM) between 5.10-9 M and 10-9 M. On the other hand, human CFU-GM were able to grow in the presence of the same T-2 toxin concentrations. IC50 were determined on day 7, 10 and 14. They were, respectively, 1.6.10-9 M; 3.6.10-9 M; 1.4.10-9 M for human cells, and 2.2.10-9 M; 3.3.10-9 M; 2.6.10 -9 M for rat cells. The present study was prompted by the need to define precisely the cytotoxic and inhibitory T-2 toxin concentrations for rat and human CFU-GM. It is particularly relevant for the investigation of cellular T-2 toxin targets and in order to elucidate the mechanism of trichothecene haematotoxicity.


2021 ◽  
Vol 17 ◽  
pp. 711-718
Author(s):  
Zafar Iqbal ◽  
Lijuan Zhai ◽  
Yuanyu Gao ◽  
Dong Tang ◽  
Xueqin Ma ◽  
...  

The diazabicyclooctane (DBO) scaffold is the backbone of non-β-lactam-based second generation β-lactamase inhibitors. As part of our efforts, we have synthesized a series of DBO derivatives A1–23 containing amidine substituents at the C2 position of the bicyclic ring. These compounds, alone and in combination with meropenem, were tested against ten bacterial strains for their antibacterial activity in vitro. All compounds did not show antibacterial activity when tested alone (MIC >64 mg/L), however, they exhibited a moderate inhibition activity in the presence of meropenem by lowering its MIC values. The compound A12 proved most potent among the other counterparts against all bacterial species with MIC from <0.125 mg/L to 2 mg/L, and is comparable to avibactam against both E. coli strains with a MIC value of <0.125 mg/L.


2020 ◽  
Vol 11 ◽  
Author(s):  
Yue Zhu ◽  
De-Yu Xie

We report to use the main protease (Mpro) of SARS-Cov-2 to screen plant flavan-3-ols and proanthocyanidins. Twelve compounds, (–)-afzelechin (AF), (–)-epiafzelechin (EAF), (+)-catechin (CA), (–)-epicatechin (EC), (+)-gallocatechin (GC), (–)-epigallocatechin (EGC), (+)-catechin-3-O-gallate (CAG), (–)-epicatechin-3-O-gallate (ECG), (–)-gallocatechin-3-O-gallate (GCG), (–)-epigallocatechin-3-O-gallate (EGCG), procyanidin A2 (PA2), and procyanidin B2 (PB2), were selected for docking simulation. The resulting data predicted that all 12 metabolites could bind to Mpro. The affinity scores of PA2 and PB2 were predicted to be −9.2, followed by ECG, GCG, EGCG, and CAG, −8.3 to −8.7, and then six flavan-3-ol aglycones, −7.0 to −7.7. Docking characterization predicted that these compounds bound to three or four subsites (S1, S1′, S2, and S4) in the binding pocket of Mpro via different spatial ways and various formation of one to four hydrogen bonds. In vitro analysis with 10 available compounds showed that CAG, ECG, GCG, EGCG, and PB2 inhibited the Mpro activity with an IC50 value, 2.98 ± 0.21, 5.21 ± 0.5, 6.38 ± 0.5, 7.51 ± 0.21, and 75.3 ± 1.29 μM, respectively, while CA, EC, EGC, GC, and PA2 did not have inhibitory activities. To further substantiate the inhibitory activities, extracts prepared from green tea (GT), two muscadine grapes (MG), cacao, and dark chocolate (DC), which are rich in CAG, ECG, GAG, EGCG, or/and PB2, were used for inhibitory assay. The resulting data showed that GT, two MG, cacao, and DC extracts inhibited the Mpro activity with an IC50 value, 2.84 ± 0.25, 29.54 ± 0.41, 29.93 ± 0.83, 153.3 ± 47.3, and 256.39 ± 66.3 μg/ml, respectively. These findings indicate that on the one hand, the structural features of flavan-3-ols are closely associated with the affinity scores; on the other hand, the galloylation and oligomeric types of flavan-3-ols are critical in creating the inhibitory activity against the Mpro activity.


1995 ◽  
Vol 31 (5-6) ◽  
pp. 185-188 ◽  
Author(s):  
C. M. E. de Wet ◽  
S. N. Venter ◽  
N. Rodda ◽  
R. Kfir ◽  
M. C. Steynberg ◽  
...  

Studies to describe the survival of Escherichia coli were performed at two sites in a river. The one site was dominated by domestic discharge and the other by industrial inputs. E coli suspensions within membrane diffusion chambers were immersed in the river at the selected sites. An identical chamber was submerged in river water in the laboratory as a comparison. Two test runs were performed, one during winter (July) and one during summer (December). Samples to determine the survival of E coli was taken on a scheduled basis. Results obtained showed no significant difference between the survival pattern of E coli as determined during the summer and winter periods or in the different parts of the river. The same survival pattern was observed for the studies performed in the laboratory.


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