The sorption of a protein-polysaccharide complex isolated from Neisseria meningitidis serogroup B on aluminum hydroxide gels and the immunological activity of the sorbed preparations

The protein-polysaccharide complex, isolated from group B N. meningitidis, is a variant of vaccine for the prophylaxis of group B N. meningitidis infection. In this investigation the influence of the complex of the physical properties of aluminium hydroxide gels, the amount of gel, pH and the duration of sorption on the process of sorption has been studied. Aluminium hydroxide has been shown to produce a stimulating effect on the response of mice to the polysaccharide and protein contained in the complex after immunization made in two injections. Gels with a smaller particle size have been found to possess greater adjuvant activity, as well as greater absorbing activity. The immunological activity of the complex, adsorbed ex tempore, has proved to be no different from that of the complex adsorbed in an hour.     

Linear oligopeptides: c.d. and n.m.r. study of Dnp-pNA derivatives of Aib-containing tetrapeptides in a β-bend conformation

A circular dichroism investigation of two β-bend forming, Aib-containing tetrapeptides, with the -Aib-l-Ala- and -l-Ala-Aib- central sequences, occurring in peptaibol antibiotics, blocked at the N-terminal end with the 2,4-dinitrophenyl group and at the C-terminal end with the p-nitroanilino group, is described. A comparison is made with a tetrapeptide containing the -l-Ala-l-Ala- central sequence, also observed in peptaibol antibiotics. The amount of β-bend conformers, determined from the intensities of the exciton couplets arising from the intramolecular interaction of the p-nitroanilino chromophores, has been assessed as a function of the hydrogen-bonding properties of the solvent. The conformational analysis in dimethylsulphoxide has been extended to ¹H nuclear magnetic resonance. Some information on the type of β-bend formed has additionally been obtained. The preparation and characterization of the three chromophoric tetrapeptides, along with some analogues and synthetic precursors, are also reported.     

A comparison of 2 methods for determining the hydrophobicity of Streptococcus groups A and B

A simple method for the evaluation of the hydrophobic properties of streptococci, pathogenic for humans, by their adherence to polystyrene and a modified method for measuring their hydrophobic properties by their sorption on hexadecane have been developed. The results obtained in the evaluation of the hydrophobic properties of streptococci by these two methods have been compared and the complete correlation of these results in classifying the cultures as hydrophobic and hydrophilic has been shown. For the first time the differences in the hydrophobic properties of different strains of group B streptococci have been established.     

In vitro adsorption of aflatoxins by means of sorbent compounds: montmorillonite

Aflatoxins are a group of mycotoxins that can be present as contaminants in a great number of food and feedstuffs. It has been demonstrated that non-nutritive adsorbent compounds are able not only to adsorb aflatoxins but also to prevent its gastrointestinal absorption. The objective of this study is to evaluate the adsorptive capacity of a montmorillonite (a natural silicate) with regard to aflatoxins, and to evaluate the efficacy and stability of the aflatoxin-montmorillonite complex in several pH, temperature and reaction media. Results have demonstrated that, at a concentration of 1% w/v, this adsorbent has a high efficacy in the sorption of aflatoxins, with mean sorption percentages higher than 98% in most of cases. Physisorption is probably the sorption mechanism of this process.     

Elfamycins: inhibitors of elongation factor‐Tu

Elfamycins are a relatively understudied group of antibiotics that target the essential process of translation through impairment of EF‐Tu function. For the most part, the utility of these compounds has been as laboratory tools for the study of EF‐Tu and the ribosome, as their poor pharmacokinetic profile and solubility has prevented implementation as therapeutic agents. However, due to the slowing of the antibiotic pipeline and the rapid emergence of resistance to approved antibiotics, this group is being reconsidered. Some researchers are using screens for novel naturally produced variants, while others are making directed, systematic chemical improvements on publically disclosed compounds. As an example of the latter approach, a GE2270 A derivative, LFF571, has completed phase 2 clinical trials, thus demonstrating the potential for elfamycins to become more prominent antibiotics in the future.     

Macrokinetics of enzyme sorption on porous beads accompanied by complex formation with an immobilized ligand

A mathematical model has been proposed for enzyme sorption on porous beads accompanied by formation of a stable complex with an immobilized ligand. It has been experimentally verified by using the system trypsin (EC 3.2.21.4) - immobilized bovine basic polyvalent trypsin inhibitor on porous silica gel. The experimental results for kinetics of the non-specific/specific trypsin sorption on a carrier agree with the model. The value of the coefficient of trypsin diffusion in macroporous silica gel was calculated.     

Update on macrolide-lincosamide-streptogramin, ketolide, and oxazolidinone resistance genes.

This Minireview summarizes the changes in the field of bacterial resistance to macrolide, lincosamide, streptogramin, ketolide, and oxazolidinone (MLSKO) antibiotics since the nomenclature review in 1999. A total of 66 genes conferring resistance to this group of antibiotics has now been identified and includes 13 new rRNA methylase genes, four ATP-binding transporter genes coding for efflux proteins, and five new inactivating enzymes. During this same time period, 73 new genera carrying known rRNA methylase genes and 87 new genera carrying known efflux and/or inactivating genes have been recognized. The number of bacteria with mutations in the genes for 23S rRNA, L4 and L22 ribosomal proteins, resulting in reduced susceptibility to some members of the group of MLSKO antibiotics has also increased and now includes nine different Gram-positive and 10 different Gram-negative genera. New conjugative transposons carrying different MLSKO genes along with an increased number of antibiotics and/or heavy metal resistance genes have been identified. These mobile elements may play a role in the continued spread of the MLSKO resistance genes into new species, genera, and ecosystems.     

Study of the association of nystatin and amphotericin B in nonaqueous solvent systems]

Association of nystatin and amphotericin B in non-aqueous systems was studied with the method of equilibria dialysis. A specially treated celophane membrane arresting colloid associats and macromolecules with a molecular weight of more than 30000 in the systems of dimethylformamide-ethylacetate was used for the dialysis. Relation between the dialysis rate and the difference of the concentrations at every side of the membrane was used for estimation of the antibiotic colloid association level. It was found that nystatin formed stable associates of the colloid type in the system of dimethylformamide-ethylacetate, close by the composition to the critical one or that providing precipitation of the antibiotic. Unlike nystatin, amphotericin B formed not colloid but larger conglomerates which precipitated. Neither of the antibiotics formed colloid associates in dimethylformamide. The level of the nystatin colloid association increased with a rise in the solution concentration and reached 80%. On the basis of the results obtained the following supposition concerning the mechanism of formation of the antibiotic complexes with polyvinylpyrrolidone (PVP) in non-aqueous systems is possible: sorption of PVP on the colloids formed or larger associates of the polyenic antibiotics must take place during coprecipitation which is accompanied by formation of a precipitate of the sorption complex.     

Interactions between bacterial membranes and peptidolipids: Lysis of Micrococcus luteus protoplasts by derivatives of peptidolipidic antibiotics from Bacillus subtilis

The lysis of protoplasts of Micrococcus luteus has been tested with various derivatives of three peptidolipidic antibiotics: iturin A, mycosubtilin and bacillomycin L. The lytic activity is dependent to the nature of the substituting group and to the position of the substituted aminoacid residue. The acetylation of OH groups leads to a decrease of the lytic activity of the natural antibiotics. The methylation of aspartyl residues of bacillomycin L gives a strong lytic activity while natural bacillomycin L has no lytic activity. The methylation of the tyrosyl residue enhances the lytic activities of iturin A and of bacillomycin L-dimethyl ester and reduces that of mycosubtilin.Correlations between the structures of derivatives and their lytic action on M. luteus protoplasts are discussed.     

Interactions between bacterial membranes and peptidolipids: lysis of micrococcus luteus protoplasts by derivatives of peptidolipidic antibiotics from bacillus subtilis.

The lysis of protoplasts of Micrococcus luteus has been tested with various derivatives of three peptidolipidic antibiotics: iturin A, mycosubtilin and bacillomycin L. The lytic activity is dependent to the nature of the substituting group and to the position of the substituted aminoacid residue. The acetylation of OH groups leads to a decrease of the lytic activity of the natural antibiotics. The methylation of aspartyl residues of bacillomycin L gives a strong lytic activity while natural bacillomycin L has no lytic activity. The methylation of the tyrosyl residue enhances the lytic activities of iturin A and of bacillomycin L-dimethyl ester and reduces that of mycosubtilin. Correlations between the structures of derivatives and their lytic action on M. luteus protoplasts are discussed.     

Optimization of the parameters that permit improvement in plate sorption activity for solid-phase immunoenzyme analysis]

The possibility of increasing the sorption activity of polystyrene plates with an initially low capacity for sorption has been shown. The qualitative and quantitative parameters of the process of physical modification have been ascertained. The empirical formula for achieving the highest degree of the sorption activity of plates by their definite exposure to ultraviolet radiation has been obtained.     

Effect of rubomycin, carminomycin and adriamycin on respiration in liver mitochondria in various metabolic states, respiratory control and ADP/O ratio

A comparative study on the effects of antitumour antibiotics of the anthracycline group (rubomycin, carminomycin and adriamycin) on respiration and oxidative phosphorylation in liver mitochondria in various metabolic states has been carried out for the first time. It was shown that the antibiotics under study cause partial inhibition of mitochondrial state 3 respiration, which is eliminated by an uncoupler. Treatment of liver mitochondria with the antibiotics decreases the ADP/O and respiratory control values and stimulates state 4 respiration. The latter is partly inhibited by oligomycin. The uncoupled respiration is decelerated in the presence of the antibiotics. Under these conditions the oxidation of succinate is inhibited by lower concentrations of the antibiotics than that of NAD+-dependent substrates. It was shown that the maximal activity is exerted by the most polar agent carminomycin, while the hydrophobic rubomycin is the least active. The experimental results are discussed in terms of the toxic effect of antitumour antibiotics.     

Inhibition of the broad spectrum nonmetallocarbapenamase of class A (NMC-A) beta-lactamase from Enterobacter cloacae by monocyclic beta-lactams.

beta-Lactamases hydrolyze beta-lactam antibiotics, a reaction that destroys their antibacterial activity. These enzymes, of which four classes are known, are the primary cause of resistance to beta-lactam antibiotics. The class A beta-lactamases form the largest group. A novel class A beta-lactamase, named the nonmetallocarbapenamase of class A (NMC-A) beta-lactamase, has been discovered recently that has a broad substrate profile that included carbapenem antibiotics. This is a serious development, since carbapenems have been relatively immune to the action of these resistance enzymes. Inhibitors for this enzyme are sought. We describe herein that a type of monobactam molecule of our design inactivates the NMC-A beta-lactamase rapidly, efficiently, and irreversibly. The mechanism of inactivation was investigated by solving the x-ray structure of the inhibited NMC-A enzyme to 1.95 A resolution. The structure shed light on the nature of the fragmentation of the inhibitor on enzyme acylation and indicated that there are two acyl-enzyme species that account for enzyme inhibition. Each of these inhibited enzyme species is trapped in a distinct local energy minimum that does not predispose the inhibitor species for deacylation, accounting for the irreversible mode of enzyme inhibition. Molecular dynamics simulations provided evidence in favor of a dynamic motion for the acyl-enzyme species, which samples a considerable conformational space prior to the entrapment of the two stable acyl-enzyme species in the local energy minima. A discussion of the likelihood of such dynamic motion for turnover of substrates during the normal catalytic processes of the enzyme is presented.     

Complete lysis of glutamic acid-producing bacteria by the use of antibiotics which inhibit the biosynthesis of cell walls.

A novel method for obtaining complete lysis of coryneform bacteria has been devised. Bacteria in the late-exponential phase of growth are treated with antibiotics which inhibit biosynthesis of the cell wall. Organisms treated in this way show increased sensitivity to lysis by added lytic enzymes. The preparation of DNA from this group of organisms is thus greatly facilitated.     

Uptake of fluoride by nano-hydroxyapatite/chitosan, a bioinorganic composite

A bioinorganic composite namely nano-hydroxyapatite/chitosan (n-HApC) composite which could be employed for technology development was prepared and studied for its defluoridation efficiency. It has been observed that there was a slight enhancement in the defluoridation capacity (DC) of n-HApC composite (1560mgF(-)/kg) than nano-hydroxyapatite (n-HAp) which has a DC of 1296mgF(-)/kg. The sorbents were characterized with XRD and TEM studies. The fluoride sorption was explained with Freundlich and Langmuir isotherms. Thermodynamic parameters such as DeltaG degrees , DeltaH degrees , DeltaS degrees and E(a) were calculated in order to understand the nature of sorption. The sorption process was found to be controlled by pseudo-second-order and pore diffusion models. Field studies were carried out with the fluoride containing water sample collected from a fluoride-endemic area in order to test the suitability of the sorbents at field conditions.     

Pseudo-isotherms for the sorption of cadmium ion onto tree fern

The kinetics of cadmium sorption on to tree fern has been investigated based on the assumption of a pseudo-second order rate law. The batch sorption model has been applied to predict the rate constant of sorption and the equilibrium capacity with the effect of initial cadmium concentration. The experimental results have been analysed by pseudo-Langmuir, pseudo-Freundlich and pseudo-Redlich–Peterson isotherms based on pseudo-second order kinetic expression constant. Both pseudo-Langmuir and pseudo-Redlich–Peterson isotherms were found to represent the measured sorption data well. According to the evaluation using the pseudo-Langmuir equation, the monolayer sorption capacity was obtained to he 16.3 mg/g. In addition, χ² analysis was also used to determine the most suitable model. Pseudo-Langmuir and pseudo-Redlich–Peterson were also the best models for the experiment data from χ² analysis.     

Evaluation of penicillin-based inhibitors of the class A and B beta-lactamases from Bacillus anthracis

Bacillus anthracis contains a class A (Bla1) and class B (Bla2) beta-lactamase, which confer resistance to beta-lactam antibiotics when expressed in Escherichia coli. In an effort to find new beta-lactamase inhibitors, several penicillin derivatives have been evaluated including experimental compounds incorporating a 6-mercaptomethyl group or a 6-pyridylmethylidene group, along with clavulanate and tazobactam, as inhibitors against Bla1 and Bla2. The 6-mercaptomethyl-substituted penicillins showed much greater activity against the zinc-containing Bla2 than Bla1. The compound that incorporated a 6-pyridylmethylidene substituent and a catecholic substituent at the 2' position was the most effective inhibitor of Bla1 with Ki=0.057 microM. Inhibitors containing iron-chelating functional groups have previously been shown to work in combination with antibiotics to inhibit growth of antibiotic-resistant bacteria expressing beta-lactamase. The development of similar compounds, incorporating these types of substituents, may help overcome resistance to currently used antibiotics.     

Structure of the UDP-glucosyltransferase GtfB that modifies the heptapeptide aglycone in the biosynthesis of vancomycin group antibiotics

BACKGROUND: Members of the vancomycin group of glycopeptide antibiotics have an oxidatively crosslinked heptapeptide scaffold decorated at the hydroxyl groups of 4-OH-Phegly4 or beta-OH-Tyr6 with mono- (residue 6) or disaccharides (residue 4). The disaccharide in vancomycin itself is L-vancosamine-1,2-glucose, and in chloroeremomycin it is L-4-epi-vancosamine-1,2-glucose. The sugars and their substituents play an important role in efficacy, particularly against vancomycin-resistant pathogenic enterococci. RESULTS: The glucosyltransferase, GtfB, that transfers the glucose residue from UDP-glucose to the 4-OH-Phegly4 residue of the vancomycin aglycone, initiating the glycosylation pathway in chloroeremomycin maturation, has been crystallized, and its structure has been determined by X-ray analysis at 1.8 A resolution. The enzyme has a two-domain structure, with a deep interdomain cleft identified as the likely site of UDP-glucose binding. A hydrophobic patch on the surface of the N-terminal domain is proposed to be the binding site of the aglycone substrate. Mutagenesis has revealed Asp332 as the best candidate for the general base in the glucosyltransfer reaction. CONCLUSIONS: The structure of GtfB places it in a growing group of glycosyltransferases, including Escherichia coli MurG and a beta-glucosyltransferase from T4 phage, which together form a subclass of the glycosyltransferase superfamily and give insights into the recognition of the NDP-sugar and aglycone cosubstrates. A single major interdomain linker between the N- and C- terminal domains suggests that reprogramming of sugar transfer or aglycone recognition in the antibiotic glycosyltransferases, including the glycopeptide and also the macrolide antibiotics, will be facilitated by this structural information.     

Moisture Sorption Isotherms of Various Tobaccos

The equilibrium moisture contents of sun-cured (Kroumougrad), flue-cured (Bright Yellow—4) and air-cured (Burley-21 and Matsukawa) tobaccos were measured over a relative humidity range from 5 to 80% at 20°C. The moisture sorption isotherms of tobaccos were of sigmoid type, and classified into two groups. In a lower humidity range below ca. 40% RH, the A group (Kroumougrad and BY-4) had a smaller moisture sorption capacity than B group (Burley-21 and Matsukawa), while in a higher humidity range above ca. 50% RH the former had a larger moisture sorption capacity than the latter. By extracting with water, the moisture content of BY-4 was increased in the lower humidity range, while it decreased in the higher humidity range. However, the moisture content of Matsukawa was scarecely changed by extracting it with water. These results suggest that the differences in equilibrium moisture content with the type of curing were due to the differences in contents of water soluble com- ponents. To control the hygroscopic properties of a tobacco, therefore, the influences of the addition of sucrose and glycerol on the equilibrium moisture content were quantitatively analysed. The moisture sorption capacity of tobacco was greatly different from its nitrogen sorption capacity. The specific surface area of tobacco calculated from moisture sorption isotherm was ca. 110 times larger than the specific surface area calculated from the nitrogen sorption isotherm. Both the nitrogen and moisture sorption data should be necessary for better understanding of the complicated sorption-desorption phenomena in tobaccos.     

两种外源抗生素在农业土壤中的吸附与迁移特性

长期施用禽畜排泄物可导致抗生素在土壤中的积累,对生态环境产生不良影响.为了解长江三角洲和珠江三角洲农业土壤中长期施用含抗生素的有机肥可能产生的环境影响,选择了7个典型农业土壤,用室内模拟方法研究了我国常用的2种抗生素(泰乐菌素和土霉素)在这些土壤中吸附和迁移行为.研究表明,抗生素在土壤中的吸附、迁移行为与抗生素种类和土壤性质有关,土壤对土霉素的吸附能力明显高于泰乐菌素.土壤对抗生素的吸附能力主要与土壤粘粒含量、有机质和氧化铁呈正相关,与其它土壤性质的相关性较小.这2类抗生素在粘质农业土壤剖面中的迁移能力较弱;但泰乐菌素在砂质土壤中较易迁移,有较大的环境风险.