6-<i>O</i>-Nucleotidyltransferase: an aminoglycoside-modifying enzyme specific for streptomycin/streptidine

Latorre, Montserrat; Revuelta, Julia; García‐Junceda, Eduardo; Bastida, Ágatha

doi:10.1039/c5md00496a

Cited by 4 publications

(8 citation statements)

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“…ANT(6′), a 37 kDa protein, transfers an adenyl group from ATP to the 6′-hydroxy function on the aminoglycoside, thus leading to a sharp decrease in the drug affinity for its target RNA. The conformational behavior of streptomycin, both in the free and the protein-bound states, was studied by NMR experiments given that the 3D structure is in a free form [ 45 , 46 ]. The streptomycin is characterized by a high degree of flexibility in solution, but this equilibrium is clearly altered upon binding to the enzyme.…”

Section: Understanding the Modifying Enzymesmentioning

confidence: 99%

Overcoming Aminoglycoside Enzymatic Resistance: Design of Novel Antibiotics and Inhibitors

et al. 2018

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Resistance to aminoglycoside antibiotics has had a profound impact on clinical practice. Despite their powerful bactericidal activity, aminoglycosides were one of the first groups of antibiotics to meet the challenge of resistance. The most prevalent source of clinically relevant resistance against these therapeutics is conferred by the enzymatic modification of the antibiotic. Therefore, a deeper knowledge of the aminoglycoside-modifying enzymes and their interactions with the antibiotics and solvent is of paramount importance in order to facilitate the design of more effective and potent inhibitors and/or novel semisynthetic aminoglycosides that are not susceptible to modifying enzymes.

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Section: Understanding the Modifying Enzymesmentioning

confidence: 99%

Overcoming Aminoglycoside Enzymatic Resistance: Design of Novel Antibiotics and Inhibitors

et al. 2018

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“…The inactivation of streptomycin could be catalyzed by ANT(6) through the transfer of the AMP group from ATP to position six of the streptidine moiety ( Latorre et al, 2016 ). In the streptomycin recognition process, positions 2, 3, and 4 in the streptose unit, position 1 in the glucose ring and positions 1 and 6 in the streptidine moiety, are in close contact with the ANT(6) protein binding residue, while positions 3–6 of the glucose unit play a minor role ( Corzana et al, 2005 ).…”

Section: Resultsmentioning

confidence: 99%

“…For instance, ANT(6) catalyzes nucleotidylylation 1 https://lpsn.dsmz.de/genus/paenibacillus of streptomycin at the hydroxyl group at position 6, and ANT(9) catalyzes nucleotidylylation of spectinomycin at the hydroxyl group at position 9. Genes coding for ANT (6) have been named ant( 6)-Ia, ant( 6)-Ib, and aadK etc. (Ramirez and Tolmasky, 2010;Hormeño et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

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Identification and characterization of a novel aminoglycoside O-nucleotidyltransferase ANT(6)-If from Paenibacillus thiaminolyticus PATH554

et al. 2023

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BackgroundPaenibacillus thiaminolyticus, a species of genus Paenibacillus of the family Paenibacillaceae, exists widely in environments and habitats in various plants and worms, and occasionally causes human infections. This work aimed to characterize the function of a novel aminoglycoside O-nucleotidyltransferase resistance gene, designated ant(6)-If, from a P. thiaminolyticus strain PATH554.MethodsMolecular cloning, antimicrobial susceptibility testing, enzyme expression and purification, and kinetic analysis were used to validate the function of the novel gene. Whole-genome sequencing and comparative genomic analysis were performed to investigate the phylogenetic relationship of ANT(6)-If and other aminoglycoside O-nucleotidyltransferases, and the synteny of ant(6)-If related sequences.ResultsThe recombinant with the cloned ant(6)-If gene (pMD19-ant(6)-If/DH5α) demonstrated a 128-fold increase of minimum inhibitory concentration level against streptomycin, compared with the control strains (DH5α and pMD19/DH5α). The kinetic parameter kcat/Km of ANT(6)-If for streptomycin was 9.01 × 103 M−1·s−1. Among the function-characterized resistance genes, ANT(6)-If shared the highest amino acid sequence identity of 75.35% with AadK. The ant(6)-If gene was located within a relatively conserved genomic region in the chromosome.Conclusionant(6)-If conferred resistance to streptomycin. The study of a novel resistance gene in an unusual environmental bacterium in this work contributed to elucidating the resistance mechanisms in the microorganisms.

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“…Altretamine, which is known for its antineoplastic properties, was also detected. 98,99 (https:// pubchem.ncbi.nlm.nih.gov/compound/5749).…”

Section: Lc-ms/ms Analysismentioning

confidence: 99%

Antimicrobial Activity against Antibiotic-resistant Pathogens and Antioxidant Activity and LCMS/MS Phytochemical Content Analysis of Selected Medicinal Plants

Thakur,

Khushboo,

Yadav

et al. 2024

J. Pure Appl. Microbiol.

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Medicinal plants are a major source of numerous therapeutic agents, and the emergence of pathogenic bacteria has rekindled interest in traditional medicine systems as an alternative approach to overcoming resistance. The dried plant material of four medicinal plants, namely Terminalia arjuna (bark), Terminalia bellirica (fruit), Aegle marmelos (leaves), and Bacopa monnieri (leaves), was powdered, and aqueous extracts were prepared. The antimicrobial activity of the extracts was evaluated against three clinically important strains: Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli 385. As E. coli 385 was resistant to the broadest spectrum of antibiotics tested, it was classified as (MDR multi-drug resistant). E. coli, Bacillus subtilis, Mycobacterium smegmatis (MTTC), and Vibrio alginolyticus (ATCC) were also assessed using the agar well diffusion method for zones of inhibition and minimum inhibitory/bactericidal concentration (MIC/MBC). Clinically important strains were found to be sensitive to the aqueous extract of T. bellerica (19.51 ± 0.61 mm) with MICs ranging from 0.31 to 0.62 mg/ml. The MDR strain was also sensitive to Bellirica monnieri (16.10 ± 0.31 mm) aqueous extract. To determine the potential for a wide range of applications, the antioxidant activities of the extracts were evaluated using DPPH, ABTS, and FRAP assays. The T. arjuna plant extract exhibited the highest radical scavenging activity with the lowest EC50 values for DPPH (1.15 ± 0.061 mg/ml) and ABTS (1.02 ± 0.07 mg/ml). The plant extracts were characterized by UV-visible spectroscopy, Fourier-transform infrared spectroscopy, and LC-MS/MS.

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6-O-Nucleotidyltransferase: an aminoglycoside-modifying enzyme specific for streptomycin/streptidine

Abstract: ANT(6) has a narrow tolerance to chemical variations in the aminoglycoside/nucleotide, making it very useful in the design of non-inactivable derivatives.

Cited by 4 publications

References 29 publications

Overcoming Aminoglycoside Enzymatic Resistance: Design of Novel Antibiotics and Inhibitors

Overcoming Aminoglycoside Enzymatic Resistance: Design of Novel Antibiotics and Inhibitors

Identification and characterization of a novel aminoglycoside O-nucleotidyltransferase ANT(6)-If from Paenibacillus thiaminolyticus PATH554

Antimicrobial Activity against Antibiotic-resistant Pathogens and Antioxidant Activity and LCMS/MS Phytochemical Content Analysis of Selected Medicinal Plants

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