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ChemPlusChem Nov 2022High-resolution mass spectrometry was used for the label-free, direct localization and relative quantification of CMC -modifications of a neomycin-sensing riboswitch...
High-resolution mass spectrometry was used for the label-free, direct localization and relative quantification of CMC -modifications of a neomycin-sensing riboswitch aptamer domain in the absence and presence of the aminoglycoside ligands neomycin B, ribostamycin, and paromomycin. The chemical probing and MS data for the free riboswitch show high exposure to solvent of the uridine nucleobases U7, U8, U13, U14, U18 as part of the proposed internal and apical loops, but those of U10 and U21 as part of the proposed internal loop were found to be far less exposed than expected. Thus, our data are in better agreement with the proposed secondary structure of the riboswitch in complexes with aminoglycosides than with that of free RNA. For the riboswitch in complexes with neomycin B, ribostamycin, and paromomycin, we found highly similar CMC -modification patterns and excellent agreement with previous NMR studies. Differences between the chemical probing and MS data in the absence and presence of the aminoglycoside ligands were quantitative rather than qualitative (i. e., the same nucleobases were labeled, but to different extents) and can be rationalized by stabilization of both the proposed bulge and the apical loop by aminoglycoside binding. Our study shows that chemical probing and mass spectrometry can provide important structural information and complement other techniques such as NMR spectroscopy.
Topics: Riboswitch; Neomycin; Ribostamycin; RNA; Paromomycin; Framycetin; Aminoglycosides; Anti-Bacterial Agents; Ligands; Oligonucleotides; Mass Spectrometry
PubMed: 36220343
DOI: 10.1002/cplu.202200256 -
Minerva Medica Apr 1982
Comparative Study
Topics: Aminoglycosides; Anti-Bacterial Agents; Dose-Response Relationship, Drug; Ear, Inner; Enzymes; Humans; Injections; Kidney; Ribostamycin
PubMed: 7070690
DOI: No ID Found -
Epidemiology and Infection Oct 2012SUMMARY We conducted an epidemic investigation to discover the route of transmission and the host factors of an outbreak of post-injection abscesses. Of the 2984...
SUMMARY We conducted an epidemic investigation to discover the route of transmission and the host factors of an outbreak of post-injection abscesses. Of the 2984 patients who visited a single clinic, 77 cases were identified and 208 age- and sex-matched controls were selected for analysis. Injected medications per se were not found to be responsible, and a deviation from safe injection practice suggested the likelihood of diluent contamination. Therefore the injected medications were classified according to whether there was a need for a diluent, and two medications showed a statistically significant association, i.e. injection with pheniramine [adjusted odds ratios (aOR) 5·93, 95% confidence interval (CI) 2·97-11·87] and ribostamycin (aOR 47·95, 95% CI 11·08-207·53). However, when considered concurrently, pheniramine lost statistical significance (aOR 8·71, 95% CI 0·44-171·61) suggesting that normal saline was the causative agent of this outbreak. Epidemiological evidence strongly suggested that this post-injection outbreak was caused by saline contaminated with Mycobacterium massiliense without direct microbiological evidence.
Topics: Abscess; Adolescent; Adult; Aged; Child; Child, Preschool; Disease Outbreaks; Drug Contamination; Female; Humans; Infant; Infant, Newborn; Injections, Intramuscular; Male; Middle Aged; Mycobacterium; Mycobacterium Infections; Republic of Korea; Young Adult
PubMed: 22217328
DOI: 10.1017/S0950268811002809 -
Il Farmaco; Edizione Pratica Oct 1981
Topics: Anti-Bacterial Agents; Humans; Ribostamycin
PubMed: 7308418
DOI: No ID Found -
Nanomedicine : Nanotechnology, Biology,... Jan 2018Delivery of biologically active proteins into cells is emerging as important strategy for many applications. Previous experiments have shown that lipoaminoglycosides...
Delivery of biologically active proteins into cells is emerging as important strategy for many applications. Previous experiments have shown that lipoaminoglycosides were capable of delivery of the anti-cytokeratin8 antibody (anti-K8) but only when formulated with lipid helpers potentially leading to toxicity from excess lipids. Here, we optimized anti-K8 delivery with various lipoaminoglycosides in the absence of a lipid helper. Results led to the identification of the aminoglycoside lipid dioleyl phosphoramido ribostamycin (DOPRI) as a potent intracellular delivery system for anti-K8. Electron microscopy revealed that delivered anti-K8 molecules were bound to intermediate filaments in cells. Anti-K8 was bound to the surface of DOPRI vesicles without perturbing lipid organization. Macropinocytosis and caveolin mediated endocytosis contributed to anti-K8 internalization and to filament labeling with a major contribution being made by the caveolin pathway. The results showed that the unique properties of DOPRI were sufficient for efficient intracellular protein delivery without requiring lipid helpers.
Topics: Anti-Bacterial Agents; Antibodies; Drug Delivery Systems; Endocytosis; HeLa Cells; Humans; Keratin-8; Ribostamycin
PubMed: 28939489
DOI: 10.1016/j.nano.2017.09.005 -
Nature Communications Jul 2015Dynamic remodelling of intersubunit bridge B2, a conserved RNA domain of the bacterial ribosome connecting helices 44 (h44) and 69 (H69) of the small and large subunit,...
Dynamic remodelling of intersubunit bridge B2, a conserved RNA domain of the bacterial ribosome connecting helices 44 (h44) and 69 (H69) of the small and large subunit, respectively, impacts translation by controlling intersubunit rotation. Here we show that aminoglycosides chemically related to neomycin-paromomycin, ribostamycin and neamine-each bind to sites within h44 and H69 to perturb bridge B2 and affect subunit rotation. Neomycin and paromomycin, which only differ by their ring-I 6'-polar group, drive subunit rotation in opposite directions. This suggests that their distinct actions hinge on the 6'-substituent and the drug's net positive charge. By solving the crystal structure of the paromomycin-ribosome complex, we observe specific contacts between the apical tip of H69 and the 6'-hydroxyl on paromomycin from within the drug's canonical h44-binding site. These results indicate that aminoglycoside actions must be framed in the context of bridge B2 and their regulation of subunit rotation.
Topics: Aminoglycosides; Anti-Bacterial Agents; Binding Sites; Escherichia coli; Escherichia coli Proteins; Framycetin; Neomycin; Paromomycin; RNA, Bacterial; Ribosome Subunits, Large, Bacterial; Ribosome Subunits, Small, Bacterial; Ribosomes; Ribostamycin; Rotation
PubMed: 26224058
DOI: 10.1038/ncomms8896 -
Biosensors & Bioelectronics Jun 2014A label-free detection method of kanamycin using aptamer-based cantilever array sensor was developed. The cantilever array was composed of sensing cantilevers and...
A label-free detection method of kanamycin using aptamer-based cantilever array sensor was developed. The cantilever array was composed of sensing cantilevers and reference cantilevers. This configuration allowed direct detection of individual cantilever deflections and subsequent determination of differential deflection of sensing/reference cantilever pair. The sensing cantilevers were functionalized with kanamycin aptamer, which was used as receptor molecules while the reference cantilevers were modified with 6-mercapto-1-hexanol (MCH) to eliminate the influence of environmental disturbances. The kanamycin-aptamer interaction induced a change in cantilever surface stress, which caused a differential deflection between the sensing and reference cantilever pair. The surface stress change was linear with kanamycin concentration over the range of 100 μM-10mM with a correlation coefficient of 0.995. A detection limit of 50 μM was obtained, at a signal-to-noise ratio of 3. The sensor also showed good selectivity against other antibiotics such as neomycin, ribostamycin and chloramphenicol. The facile method for kanamycin detection may have great potential for investigating more other molecules.
Topics: Anti-Bacterial Agents; Aptamers, Nucleotide; Biosensing Techniques; Equipment Design; Hexanols; Kanamycin; Limit of Detection; Microarray Analysis; Signal-To-Noise Ratio; Sulfhydryl Compounds
PubMed: 24480130
DOI: 10.1016/j.bios.2013.12.068 -
The Japanese Journal of Antibiotics Aug 1976The MICs of ribostamycin (RSM) were determined by the two-fold serial agar-dilution method of 109 bacterial strains of 20 species. The diameters of inhibition zones of...
The MICs of ribostamycin (RSM) were determined by the two-fold serial agar-dilution method of 109 bacterial strains of 20 species. The diameters of inhibition zones of these bacterial strains by the 50 mug RSM disc were also measured. The relation between the MIC and the diameter of the inhibition zone was found to be expressed as a primary regression line in all cases of the conventional method (cultured for about 16 hours), delayed assay method (cultured for about 24 hours) and rapid methods (5 approximately 6 hours and 3 approximately 4 hours culture methods). Thus, it was confirmed that the single-disc method can be employed for the susceptibility test of RSM. Subsequently, variations of MICs obtained by the disc-diffusion method were compared with those obtained by the serial agar-dilution method.
Topics: Anti-Bacterial Agents; Bacteria; Microbial Sensitivity Tests; Ribostamycin
PubMed: 957521
DOI: No ID Found -
The Journal of Antimicrobial... Oct 2021To describe a novel chromosomal aminoglycoside phosphotransferase named APH(3')-IId identified in an MDR Brucella intermedia ZJ499 isolate from a cancer patient.
OBJECTIVES
To describe a novel chromosomal aminoglycoside phosphotransferase named APH(3')-IId identified in an MDR Brucella intermedia ZJ499 isolate from a cancer patient.
METHODS
Species identity was determined by PCR and MALDI-TOF MS analysis. WGS was performed to determine the genetic elements conferring antimicrobial resistance. Gene cloning, transcriptional analysis and targeted gene deletion, as well as protein purification and kinetic analysis, were performed to investigate the mechanism of resistance.
RESULTS
APH(3')-IId consists of 266 amino acids and shares the highest identity (48.25%) with the previously known APH(3')-IIb. Expression of aph(3')-IId in Escherichia coli decreased susceptibility to kanamycin, neomycin, paromomycin and ribostamycin. The aph(3')-IId gene in ZJ499 was transcriptionally active under laboratory conditions and the relative abundance of this transcript was unaffected by treatment with the above four antibiotics. However, deletion of aph(3')-IId in ZJ499 results in decreased MICs of these drugs. The purified APH(3')-IId showed phosphotransferase activity against kanamycin, neomycin, paromomycin and ribostamycin, with catalytic efficiencies (kcat/Km) ranging from ∼105 to 107 M-1 s-1. Genetic environment and comparative genomic analyses suggested that aph(3')-IId is probably a ubiquitous gene in Brucella, with no mobile genetic elements detected in its surrounding region.
CONCLUSIONS
APH(3')-IId is a novel chromosomal aminoglycoside phosphotransferase and plays an important role in the resistance of B. intermedia ZJ499 to kanamycin, neomycin, paromomycin and ribostamycin. To the best of our knowledge, APH(3')-IId represents the fourth characterized example of an APH(3')-II enzyme.
Topics: Aminoglycosides; Anti-Bacterial Agents; Brucella; Drug Resistance, Multiple, Bacterial; Humans; Kanamycin; Kanamycin Kinase; Kinetics
PubMed: 34329431
DOI: 10.1093/jac/dkab272 -
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