Metal ion interaction with penicillins— part VII: Mixed-ligand complex formation of cobalt(II), nickel(II), copper(II), and zinc(II) with amplicillin and nucleic bases
TL;DR: Equilibrium study on the mixed-ligand complex formation of M2+ ions with alpha-d-(-)aminobenzyl penicillin popularly known as ampicillin and nucleic bases and stability constants of the ternary complexes.
Abstract: Equilibrium study on the mixed-ligand complex formation of M2+ ions (M = Co, Ni, Cu, and Zn) with alpha-d-(-)aminobenzyl penicillin popularly known as ampicillin, (hereafter, ampH +/-), and nucleic bases, viz. adenine, guanine, thymine, uracil, and cytosine (B), in aqueous solution at 37 degrees C at a fixed ionic strength, I = 0.1 M (NaNO3) indicates the formation of complexes of the types: M(amp), M(B), M(amp)(B), M(H-1 amp)(B), and M(H-1 amp)(B)(OH). Stability constants of the ternary complexes are in the order: Co2+ Zn2+ with regard to the mental ions and guanine > adenine > uracil > thymine > cytosine with regard to the nucleic bases. Complex formation equilibria have been worked out on the basis of species distribution curves.
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TL;DR: The present review examines the evidence for the significance of co-selection for antibiotic resistance among bacteria exposed to biocides used as disinfectants, antiseptics and preservatives, and to heavy metals used as growth promoters and therapeutic agents for some livestock species.
Abstract: Concerns have been raised in recent years regarding co-selection for antibiotic resistance among bacteria exposed to biocides used as disinfectants, antiseptics and preservatives, and to heavy metals (particularly copper and zinc) used as growth promoters and therapeutic agents for some livestock species. There is indeed experimental and observational evidence that exposure to these non-antibiotic antimicrobial agents can induce or select for bacterial adaptations that result in decreased susceptibility to one or more antibiotics. This may occur via cellular mechanisms that are protective across multiple classes of antimicrobial agents or by selection of genetic determinants for resistance to non-antibiotic agents that are linked to genes for antibiotic resistance. There may also be relevant effects of these antimicrobial agents on bacterial community structure and via non-specific mechanisms such as mobilization of genetic elements or mutagenesis. Notably, some co-selective adaptations have adverse effects on fitness in the absence of a continued selective pressure. The present review examines the evidence for the significance of these phenomena, particularly in respect of bacterial zoonotic agents that commonly occur in livestock and that may be transmitted, directly or via the food chain, to human populations.
266 citations
TL;DR: The presence of mercury was significantly associated with low antimicrobial resistance rates of Escherichia coli against β-lactams, aminoglycosides and other antibiotics, and effects of subinhibitory concentrations of mercury on bacterial resistance against penicillins, cephalosporins, am inoglycoside and doxycycline were demonstrated in a laboratory trial.
Abstract: Heavy metals are regularly found in liquid pig manure, and might interact with bacterial antimicrobial resistance Concentrations of heavy metals were determined by atomic spectroscopic methods in 305 pig manure samples and were connected to the phenotypic resistance of Escherichia coli (n=613) against 29 antimicrobial drugs Concentrations of heavy metals (/kg dry matter) were 008-530 mg cadmium, 11-320 mg chrome, 224-33876 mg copper, <20-267 mg lead, <001-011 mg mercury, 31-973 mg nickel and 930-82390 mg zinc Associated with the detection of copper and zinc, resistance rates against β-lactams were significantly elevated By contrast, the presence of mercury was significantly associated with low antimicrobial resistance rates of Escherichia coli against β-lactams, aminoglycosides and other antibiotics Effects of subinhibitory concentrations of mercury on bacterial resistance against penicillins, cephalosporins, aminoglycosides and doxycycline were also demonstrated in a laboratory trial Antimicrobial resistance in the porcine microflora might be increased by copper and zinc By contrast, the occurrence of mercury in the environment might, due to co-toxicity, act counter-selective against antimicrobial resistant strains
183 citations
Cites background from "Metal ion interaction with penicill..."
...Copper is known to affect the stability of ampicillin (Fernández-González et al., 2005; Mukherjee and Ghosh, 1995) and other penicillins, at least in a concentration of 3....
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..., 1985); zinc and copper affect the stability of ampicillin (Beard et al., 1992; FernándezGonzález et al., 2005; Mukherjee and Ghosh, 1995)....
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...…heavy metal cations complex with antibiotic substances, e.g. tetracyclines (Palm et al., 2008), thus inhibiting their intestinal absorption (Brion et al., 1985); zinc and copper affect the stability of ampicillin (Beard et al., 1992; FernándezGonzález et al., 2005; Mukherjee and Ghosh, 1995)....
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...Copper is known to affect the stability of ampicillin (Fernández-González et al., 2005; Mukherjee and Ghosh, 1995) and other penicillins, at least in a concentration of 3.15 mM (Beard et al., 1992)....
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TL;DR: Characterization of subclones of E. coli clones in animals supplemented with zinc suggests an increase in antimicrobial resistance due to influences on plasmid uptake by zinc supplementation, questioning the reasonability of zinc feed additives as a result of the ban of antimicrobial growth promoters.
Abstract: Following the Europe-wide ban of antimicrobial growth promoters, feed supplementation with zinc has increased in livestock breeding. In addition to possible beneficial effects on animal health, feed supplementation with heavy metals is known to influence the gut microbiota and might promote the spread of antimicrobial resistance via co-selection or other mechanisms. As Escherichia coli is among the most important pathogens in pig production and often displays multi-resistant phenotypes, we set out to investigate the influence of zinc feed additives on the composition of the E. coli populations in vivo focusing on phylogenetic diversity and antimicrobial resistance. In a piglet feeding trial, E. coli were isolated from ileum and colon digesta of high dose zinc-supplemented (2500ppm) and background dose (50ppm) piglets (control group). The E. coli population was characterized via pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST) for the determination of the phylogenetic background. Phenotypic resistance screening via agar disk diffusion and minimum inhibitory concentration testing was followed by detection of resistance genes for selected clones. We observed a higher diversity of E. coli clones in animals supplemented with zinc compared to the background control group. The proportion of multi-resistant E. coli was significantly increased in the zinc group compared to the control group (18.6% vs. 0%). For several subclones present both in the feeding and the control group we detected up to three additional phenotypic and genotypic resistances in the subclones from the zinc feeding group. Characterization of these subclones suggests an increase in antimicrobial resistance due to influences on plasmid uptake by zinc supplementation, questioning the reasonability of zinc feed additives as a result of the ban of antimicrobial growth promoters.
153 citations
TL;DR: Zn22+ elimination is shown to be a more precise method of depleting Zn2+ than by using the chelator N,N,N′, N′-tetrakis(2-pyridylmethyl)ethylenediamine.
Abstract: Zinc ions play indispensable roles in biological chemistry. However, bacteria have an impressive ability to acquire Zn2+ from the environment, making it exceptionally difficult to achieve Zn2+ deficiency, and so a comprehensive understanding of the importance of Zn2+ has not been attained. Reduction of the Zn2+ content of Escherichia coli growth medium to 60 nm or less is reported here for the first time, without recourse to chelators of poor specificity. Cells grown in Zn2+-deficient medium had a reduced growth rate and contained up to five times less cellular Zn2+. To understand global responses to Zn2+ deficiency, microarray analysis was conducted of cells grown under Zn2+-replete and Zn2+-depleted conditions in chemostat cultures. Nine genes were up-regulated more than 2-fold (p < 0.05) in cells from Zn2+-deficient chemostats, including zinT (yodA). zinT is shown to be regulated by Zur (zinc uptake regulator). A mutant lacking zinT displayed a growth defect and a 3-fold lowered cellular Zn2+ level under Zn2+ limitation. The purified ZinT protein possessed a single, high affinity metal-binding site that can accommodate Zn2+ or Cd2+. A further up-regulated gene, ykgM, is believed to encode a non-Zn2+ finger-containing paralogue of the Zn2+ finger ribosomal protein L31. The gene encoding the periplasmic Zn2+-binding protein znuA showed increased expression. During both batch and chemostat growth, cells “found” more Zn2+ than was originally added to the culture, presumably because of leaching from the culture vessel. Zn2+ elimination is shown to be a more precise method of depleting Zn2+ than by using the chelator N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine.
136 citations
TL;DR: A survey of recent evidences supporting the use of a variety of metal ligands, and even functionalized nanoparticles, for the treatment of the most common ND, finding that the beneficial neuropharmacological actions of metal‐targeted agents most likely arise from local metal redistribution rather than from massive metal removal.
Abstract: Mounting evidence suggests a central role for transition biometals in the etiopathogenesis of neurodegenerative diseases (ND). Indeed, while studying the molecular basis for this heterogeneous group of diseases, it has become increasingly evident that biometals and nonphysiological Al are often involved in pathology onset and progression, either by affecting the conformation of specific proteins or by exacerbating local oxidative stress. The apparently critical role played by metal dishomeostasis in ND makes chelation therapy an attractive pharmacological option. However, classical metal chelation approaches, relying on potent metal ligands, turned out to be successful only in those rare cases where exceptional brain metal accumulation occurs due to specific defects in metal metabolism. In contrast, metal-targeted approaches using ligand of intermediate strength seem to be more appropriate in fighting the major ND, although their benefits are still questioned. We report here a survey of recent evidences supporting the use of a variety of metal ligands, and even functionalized nanoparticles, for the treatment of the most common ND. The beneficial neuropharmacological actions of metal-targeted agents most likely arise from local metal redistribution rather than from massive metal removal. The perspectives for the development of new effective agents against ND are critically discussed.
85 citations
References
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1,459 citations
TL;DR: In this article, the driving forces leading to the formation of ternary Cu2+ complexes are outlined; they are (i) statistical reasons, neutralization of charge in the mixed-ligand complexes, steric factors (bulky groups, ring size of chelates), and formation of π bonds.
Abstract: The driving forces leading to the formation of ternary Cu2+ complexes are outlined; they are (i) statistical reasons, (ii) neutralization of charge in the mixed-ligand complexes, (iii) steric factors (bulky groups, ring size of chelates), and (iv) formation of π bonds. The last point is important for achieving a large stability, as well as for the observation of discriminating qualities. An additional stability increase may possibly be achieved through a direct interaction between the two ligands bound to the same metal ion, i.e. Schiff base formation, hydrogen bonding or a charge-transfer relation. The latter leads to distinct structures, i.e. metal ion-bridged charge-transfer complexes. The relation between stability and structure on the reactivity of mixed-ligand complexes is emphasized. The relevance of the results for mixed-ligand complexes containing metal ions other than Cu2+ is briefly outlined.
301 citations
TL;DR: The program, which employs the non-linear least-squares method, may be used to calculate equilibrium constants for hydrolysed metal ions, protonated ligands, and simple, Protonated, Hydrolysed, polynuclear, and mixed complexes.
Abstract: A general computer program is described for the interpretation of pH titration data for mixtures containing the ions of up to two metals and up to two ligands. The program, which employs the non-linear least-squares method, may be used to calculate equilibrium constants for hydrolysed metal ions, protonated ligands, and simple, protonated, hydrolysed, polynuclear, and mixed complexes.
297 citations
TL;DR: Various divalent metal ions have been added in 10−4 M concentration to solutions of calf-thymus DNA in 5 × 10−3 M sodium nitrate, finding that the double-stranded helical configuration of DNA is stable in solutions containing as low as 10−2 M concentration of electrolyte.
Abstract: RECENTLY there has been considerable interest in the interaction of metal ions with nucleic acids and polynucleotides, primarily as a consequence of the fact that the hydrogen-bonded structure of these macro-molecules collapses in solution in the absence of metallic salts1–4. It is perhaps of equal importance that some metal ions are as effective in destroying the native structure of deoxyribonucleic acid (DNA) as others are in maintaining it. Such destabilization has previously remained largely undetected because investigations of metal interactions with DNA have generally been carried out in approximately 0.1 M solution of an electrolyte such as sodium chloride, in which the destabilization effects are masked5. However, the double-stranded helical configuration of DNA is stable in solutions containing as low as 10−3 M concentration of electrolyte6. In the present work, various divalent metal ions have been added in 10−4 M concentration to solutions of calf-thymus DNA (5 × 10−5 M in phosphate) in 5 × 10−3 M sodium nitrate. Changes in optical density at 260 mµ ara then observed in a Beckman DU spectrophotometer on heating these solutions at the rate of 1° per min. to 90° and then cooling at the same rate7. The conversion of the low optical density solution to the high optical density solution is correlated with the transformation of the double-stranded helix to single strands, and the mean temperature of transition (Tm) is a measure of the stability of the molecule7.
220 citations
TL;DR: Phenylalanine is a strong competitor of the incorporation of leucine promoted by poly U and related polynucleotides, and becomes more effective for polylysine synthesis as the temperature is raised from 20 to 45°C and the Mg 2+ concentration is slightly increased.
Abstract: Polyribothymidylic acid promotes incorporation of phenylalanine into acid-insoluble products in a cell-free Escherichia coli system. Under conditions in which poly U‡ exists as a random coil, poly rT possesses considerable ordered structure. The structural differences between the two polymers are reflected in their respective effects on phenylalanine incorporation at different temperatures. At 20°C poly rT is much less effective than poly U, probably because its ordered structure interferes with ribosomal attachment. At 45°C, when it exists as a random coil, poly rT promotes phenylalanine incorporation at a higher initial rate than does poly U. This may be ascribed to a higher complexing ability of the former polymer, facilitating its interaction with the adaptors of phenylalanine transfer RNA. The effect of temperature and Mg2+ concentration, factors that affect interaction between poly- and oligonucleotides, on the promotion of incorporation of leucine and phenylalanine by poly U was examined. This apparent “ambiguity” becomes more pronounced with conditions that increase the complexing ability of the polymers. It is higher with poly rT than with poly U and increases in either case with decreased temperature or increased Mg2+ concentration. These conditions also lead to significant incorporation of amino acids (isoleucine, serine, tyrosine) that, like leucine, have two TPs in their code triplets. With low Mg2+ (0·01 M ), or in the presence of excess unlabeled phenylalanine and transfer RNA, poly U promotes the incorporation of phenylalanine but not that of leucine, i.e. the “ambiguity” disappears. Phenylalanine is a strong competitor of the incorporation of leucine promoted by poly U and related polynucleotides. Polyadenylic acid becomes more effective for polylysine synthesis as the temperature is raised from 20 to 45°C and the Mg2+ concentration is slightly increased. Facilitation of ribosomal attachment through partial disorganization of the secondary structure of this polynucleotide may be largely responsible for this effect.
175 citations