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The Journal of Antibiotics Apr 1976
Topics: Anti-Bacterial Agents; Butirosin Sulfate; Cyclohexanols; Gentamicins; Kanamycin; Neomycin; Paromomycin; Ribostamycin; Sisomicin; Spectinomycin; Streptomycin
PubMed: 58858
DOI: 10.7164/antibiotics.29.319 -
Frontiers in Microbiology 2023species have been identified as agents responsible for various diseases in both humans and animals. Multidrug-resistant strains pose a significant public health threat...
BACKGROUND
species have been identified as agents responsible for various diseases in both humans and animals. Multidrug-resistant strains pose a significant public health threat due to their emergence and spread in clinical settings and the environment. The aim of this study was to determine a novel resistance mechanism against aminoglycoside antimicrobials in a clinical isolate.
METHODS
The function of was verified by gene cloning and antibiotic susceptibility tests. To explore the activity of the enzyme, recombinant proteins were expressed, and enzyme kinetics were tested. To determine the molecular background and mechanism of , whole-genome sequencing and bioinformatic analysis were performed.
RESULTS
The novel aminoglycoside -acetyltransferase gene confers resistance to several aminoglycosides. Among the antimicrobials tested, ribostamycin showed the highest increase (128-fold) in the minimum inhibitory concentration (MIC) compared with the control strains. According to the MIC results of the cloned , AAC(6')-Va also showed the highest catalytic efficiency for ribostamycin [/ ratio = (3.35 ± 0.17) × 10 M s]. Sharing the highest amino acid identity of 54.68% with AAC(6')-VaIc, the novel aminoglycoside -acetyltransferase constituted a new branch of the AAC(6') family due to its different resistance profiles. The gene context of and its close relatives was conserved in the genomes of species of the genus .
CONCLUSION
The novel resistance gene confers resistance to several aminoglycosides, especially ribostamycin. Our finding of a novel resistance gene in clinical will help us develop more effective treatments for this pathogen's infections.
PubMed: 37920263
DOI: 10.3389/fmicb.2023.1229593 -
The Journal of Antibiotics Nov 1975The aminoglycoside phosphotransferase of Pseudomonas aeruginosa 21-75 was purified by affinity chromatography using dibekacin-Sephadex 4B or lividomycin A-Sepharose 4B...
The aminoglycoside phosphotransferase of Pseudomonas aeruginosa 21-75 was purified by affinity chromatography using dibekacin-Sephadex 4B or lividomycin A-Sepharose 4B followed by DEAE Sephadex A-50 chromatography. It had activities of both the known aminoglycoside 3'-phosphotransferases I and II, and transferred phosphate from ATP to the 3'-hydroxyl group of kanamycin A, ribostamycin and butirosin A and 5-hydroxyl group of lividomycin A. This enzyme was designated aminoglycoside 3'-phosphotransferase III. It showed strong substrate inhibition by kanamycin A and ribostamycin when their concentration exceeded 6 muM. Purification and characterization of this enzyme are reported.
Topics: Aminoglycosides; Butirosin Sulfate; Kanamycin; Paromomycin; Phosphotransferases; Pseudomonas aeruginosa; Ribostamycin
PubMed: 53228
DOI: 10.7164/antibiotics.28.845 -
Nucleic Acids Research Nov 2018A synthetic riboswitch N1, inserted into the 5'-untranslated mRNA region of yeast, regulates gene expression upon binding ribostamycin and neomycin. Interestingly, a...
A synthetic riboswitch N1, inserted into the 5'-untranslated mRNA region of yeast, regulates gene expression upon binding ribostamycin and neomycin. Interestingly, a similar aminoglycoside, paromomycin, differing from neomycin by only one substituent (amino versus hydroxyl), also binds to the N1 riboswitch, but without affecting gene expression, despite NMR evidence that the N1 riboswitch binds all aminoglycosides in a similar way. Here, to explore the details of structural dynamics of the aminoglycoside-N1 riboswitch complexes, we applied all-atom molecular dynamics (MD) and temperature replica-exchange MD simulations in explicit solvent. Indeed, we found that ribostamycin and neomycin affect riboswitch dynamics similarly but paromomycin allows for more flexibility because its complex lacks the contact between the distinctive 6' hydroxyl group and the G9 phosphate. Instead, a transient hydrogen bond of 6'-OH with A17 is formed, which partially diminishes interactions between the bulge and apical loop of the riboswitch, likely contributing to riboswitch inactivity. In many ways, the paromomycin complex mimics the conformations, interactions, and Na+ distribution of the free riboswitch. The MD-derived interaction network helps understand why riboswitch activity depends on aminoglycoside type, whereas for another aminoglycoside-binding site, aminoacyl-tRNA site in 16S rRNA, activity is not discriminatory.
Topics: Aminoglycosides; Binding Sites; Molecular Conformation; Molecular Dynamics Simulation; Neomycin; Paromomycin; Ribostamycin; Riboswitch
PubMed: 30239867
DOI: 10.1093/nar/gky833 -
Frontiers in Veterinary Science 2023Ramie (, BN) is used as livestock forage through suitable silage fermentation owing to its nutritional value. To date, relatively few studies have investigated the...
Ramie (, BN) is used as livestock forage through suitable silage fermentation owing to its nutritional value. To date, relatively few studies have investigated the effects of dietary fermented BN (FBN) on gut health in finishing pigs. The aim of the present study was to investigate the effects of dietary supplementation with 20% FBN on intestinal morphology, gene expression, and the functional response of the gut microbiota in finishing pigs. We found that FBN did not significantly affect serum antioxidant enzyme activities, ileal morphology, or the expression of genes encoding antioxidant enzymes, inflammatory cytokines, or tight junction proteins in the liver of the pigs. However, the gene expression levels of aryl hydrocarbon receptor () and interleukin 6 () were significantly downregulated in the ileum. A metagenomic analysis demonstrated that, compared with that seen in the control group, the cecal microbiota of pigs in the FBN treatment group was more closely clustered and contained a greater number of unique microbes. Bacteria were the predominant kingdom in the cecal microbiota, while Firmicutes, Bacteroidetes, and Proteobacteria were the dominant phyla, and , , and were the dominant genera. Dietary FBN significantly increased the abundance of the probiotic bacterium ( < 0.05). Functional analysis of the cecal microbiota showed that ABC transporter levels and glycolysis/gluconeogenesis-associated functions were diminished in FBN-fed pigs. Meanwhile, CAZyme analysis revealed that dietary FBN significantly downregulated the contents of carbohydrate-active enzymes, such as GT2, GH1, GH25, and GH13_31. In addition, cytochrome P450 analysis revealed that the abundance of CYP51 and CYP512 decreased with FBN treatment. An assessment of antibiotic resistance based on the Comprehensive Antibiotic Resistance Database (CARD) annotation indicated that the cecal microbes from pigs in the FBN treatment group had increased resistance to lincosamide, streptogramin, and chloramphenicol and reduced resistance to amikacin, isepamicin, neomycin, lividomycin, gentamicin, paromomycin, ribostamycin, and butirosin. Finally, virulence factor-related analysis showed that putative hemolysin-associated functions were decreased, whereas fibronectin-binding protein, flagella, and alginate-associated functions were increased. Taken together, our data showed that FBN supplementation exerted only minor effects on intestinal morphology and microbial community composition, suggesting that it is potentially safe for use as a supplement in the diets of finishing pigs. However, more studies are needed to validate its functionality.
PubMed: 37841475
DOI: 10.3389/fvets.2023.1253778 -
Angewandte Chemie (International Ed. in... Aug 2010
Topics: Ligands; Magnetic Resonance Spectroscopy; Nucleic Acid Conformation; RNA; Ribostamycin; Riboswitch; Temperature
PubMed: 20632338
DOI: 10.1002/anie.201001339 -
Giornale Italiano Di Dermatologia E... Oct 1987
Comparative Study
Topics: Administration, Topical; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Child; Child, Preschool; Female; Humans; Male; Middle Aged; Ribostamycin; Skin Diseases, Infectious; Staphylococcal Infections; Streptococcal Infections
PubMed: 3443457
DOI: No ID Found -
Biochemistry Oct 2011Recognition of nucleic acids is important for our understanding of nucleic acid structure as well as for our understanding of nucleic acid-protein interactions. In... (Comparative Study)
Comparative Study
Recognition of nucleic acids is important for our understanding of nucleic acid structure as well as for our understanding of nucleic acid-protein interactions. In addition to the direct readout mechanisms of nucleic acids such as H-bonding, shape recognition of nucleic acids is being increasingly recognized as playing an equally important role in DNA recognition. Competition dialysis, UV, flourescent intercalator displacement (FID), computational docking, and calorimetry studies were conducted to study the interaction of neomycin with a variety of nucleic acid conformations (shapes). At pH 5.5, the results suggest the following. (1) Neomycin binds three RNA structures [16S A site rRNA, poly(rA)·poly(rA), and poly(rA)·poly(rU)] with high affinities (K(a) ~ 10(7) M(-1)). (2) The binding of neomycin to A-form GC-rich oligomer d(A(2)G(15)C(15)T(2))(2) has an affinity comparable to those of RNA structures. (3) The binding of neomycin to DNA·RNA hybrids shows a 3-fold variance that can be attributed to their structural differences [for poly(dA)·poly(rU), K(a) = 9.4 × 10(6) M(-1), and for poly(rA)·poly(dT), K(a) = 3.1 × 10(6) M(-1)]. (4) The interaction of neomycin with DNA triplex poly(dA)·2poly(dT) yields a binding affinity (K(a)) of 2.4 × 10(5) M(-1). (5) Poly(dA-dT)(2) shows the lowest association constant for all nucleic acids studied (K(a) < 10(5)). (6) Neomycin binds to G-quadruplexes with K(a) values of ~10(4)-10(5) M(-1). (7) Computational studies show that the decrease in major groove width in the B to A transition correlates with increasing neomycin affinity. Neomycin's affinity for various nucleic acid structures can be ranked as follows: RNAs and GC-rich d(A(2)G(15)C(15)T(2))(2) structures > poly(dA)·poly(rU) > poly(rA)·poly(dT) > T·A-T triplex, G-quadruplex, B-form AT-rich, or GC-rich DNA sequences. The results illustrate the first example of a small molecule-based "shape readout" of different nucleic acid conformations.
Topics: Aminoglycosides; Animals; Binding, Competitive; Cattle; DNA; DNA, A-Form; DNA, B-Form; Fluoresceins; Neomycin; Nucleic Acid Conformation; Nucleic Acid Heteroduplexes; Nucleic Acids; Paromomycin; Polynucleotides; Ribostamycin; Thermodynamics
PubMed: 21863895
DOI: 10.1021/bi201077h -
ACS Infectious Diseases Oct 2019A series of derivatives of the 4,5-disubstituted class of 2-deoxystreptamine aminoglycoside antibiotics neomycin, paromomycin, and ribostamycin was prepared and assayed...
Modification at the 2'-Position of the 4,5-Series of 2-Deoxystreptamine Aminoglycoside Antibiotics To Resist Aminoglycoside Modifying Enzymes and Increase Ribosomal Target Selectivity.
A series of derivatives of the 4,5-disubstituted class of 2-deoxystreptamine aminoglycoside antibiotics neomycin, paromomycin, and ribostamycin was prepared and assayed for (i) their ability to inhibit protein synthesis by bacterial ribosomes and by engineered bacterial ribosomes carrying eukaryotic decoding A sites, (ii) antibacterial activity against wild type Gram negative and positive pathogens, and (iii) overcoming resistance due to the presence of aminoacyl transferases acting at the 2'-position. The presence of five suitably positioned residual basic amino groups was found to be necessary for activity to be retained upon removal or alkylation of the 2'-position amine. As alkylation of the 2'-amino group overcomes the action of resistance determinants acting at that position and in addition results in increased selectivity for the prokaryotic over eukaryotic ribosomes, it constitutes an attractive modification for introduction into next generation aminoglycosides. In the neomycin series, the installation of small (formamide) or basic (glycinamide) amido groups on the 2'-amino group is tolerated.
Topics: Aminoglycosides; Anti-Bacterial Agents; Bacteria; Binding Sites; Drug Resistance, Multiple, Bacterial; Hexosamines; Humans; Microbial Sensitivity Tests; Neomycin; Paromomycin; Protein Biosynthesis; Ribosomes; Structure-Activity Relationship
PubMed: 31436080
DOI: 10.1021/acsinfecdis.9b00128 -
Il Farmaco; Edizione Pratica Oct 1981
Topics: Adult; Anti-Bacterial Agents; Female; Humans; Male; Ribostamycin
PubMed: 7308419
DOI: No ID Found