Mechanisms of resistance to aminoglycoside antibiotics: overview and perspectives
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TLDR
By far the most widespread mechanism of resistance to AGs is the inactivation of these antibiotics by AG-modifying enzymes, and an overview of these mechanisms is provided.Abstract:
Aminoglycoside (AG) antibiotics are used to treat many Gram-negative and some Gram-positive infections and, importantly, multidrug-resistant tuberculosis. Among various bacterial species, resistance to AGs arises through a variety of intrinsic and acquired mechanisms. The bacterial cell wall serves as a natural barrier for small molecules such as AGs and may be further fortified via acquired mutations. Efflux pumps work to expel AGs from bacterial cells, and modifications here too may cause further resistance to AGs. Mutations in the ribosomal target of AGs, while rare, also contribute to resistance. Of growing clinical prominence is resistance caused by ribosome methyltransferases. By far the most widespread mechanism of resistance to AGs is the inactivation of these antibiotics by AG-modifying enzymes. We provide here an overview of these mechanisms by which bacteria become resistant to AGs and discuss their prevalence and potential for clinical relevance.read more
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Vibrios from the Norwegian marine environment: Characterization of associated antibiotic resistance and virulence genes
Fredrik Håkonsholm,Bjørn Tore Lunestad,Jose Roberto Aguirre Sánchez,Jaime Martinez-Urtaza,Nachiket P. Marathe,Cecilie Smith Svanevik +5 more
TL;DR: Low prevalence of multidrug resistance and absence of virulence genes of high global concern among environmental vibrios in Norway is shown, however, in the light of climate change, and projected rising sea surface temperatures, even in the cold temperate areas, there is a need for frequent monitoring of resistance and virulence in vibrio to be prepared for future public health challenges.
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L-lysine potentiates aminoglycosides against Acinetobacter baumannii via regulation of proton motive force and antibiotics uptake.
Wanyan Deng,Tiwei Fu,Zhen Zhang,Xiao Jiang,Jianping Xie,Hang Sun,Peng Hu,Hong Ren,Pei-Fu Zhou,Qi Liu,Quanxin Long +10 more
TL;DR: Exogenous L-lysine can increase proton motive force via transmembrane chemical gradient, resulting in aminoglycoside acumination that further accounts for reactive oxygen species production and highlights a promising strategy against bacterial infection.
Journal ArticleDOI
Apralogs: Apramycin 5-O-Glycosides and Ethers with Improved Antibacterial Activity and Ribosomal Selectivity and Reduced Susceptibility to the Aminoacyltranserferase (3)-IV Resistance Determinant.
Jonathan C. K. Quirke,Parasuraman Rajasekaran,Parasuraman Rajasekaran,Vikram A. Sarpe,Vikram A. Sarpe,Amr Sonousi,Ivan Osinnii,Marina Gysin,Klara Haldimann,Qiao-Jun Fang,Dimitri Shcherbakov,Sven N. Hobbie,Su-Hua Sha,Jochen Schacht,Andrea Vasella,Erik C. Böttger,David Crich +16 more
TL;DR: The design, synthesis, and evaluation of three series of apramycin derivatives are described, all functionalized at the 5-position, with the goals of increasing the antibacterial potency without sacrificing selectivity between bacterial and eukaryotic ribosomes, and of overcoming the rare aminoglycoside acetyltransferase (3)-IV class of aminglycoside-modifying enzymes.
Journal ArticleDOI
Effects of the 1-N-(4-Amino-2S-hydroxybutyryl) and 6′-N-(2-Hydroxyethyl) Substituents on Ribosomal Selectivity, Cochleotoxicity, and Antibacterial Activity in the Sisomicin Class of Aminoglycoside Antibiotics
Amr Sonousi,Vikram A. Sarpe,Margarita Brilkova,Jochen Schacht,Andrea Vasella,Erik C. Böttger,David Crich +6 more
TL;DR: The prediction that plazomicin will exhibit ototoxicity comparable to those of the parent and the current clinical aminoglycoside antibiotics gentamicin and tobramycin is borne out by ex vivo studies with mouse cochlear explants.
Journal ArticleDOI
Fate of bacterial community, antibiotic resistance genes and gentamicin residues in soil after three-year amendment using gentamicin fermentation waste.
Zhaojun Li,Yuanwang Liu,Dengmiao Cheng,Jianming Xue,Yao Feng,Steve A. Wakelin,Louise Weaver,Ebrahim Shehata,Zhaojun Li +8 more
TL;DR: In this paper, the impacts of composted and raw gentamicin fermentation waste (GFW) application to land on residual soil pH, physicochemical properties, bacterial community composition, and antibiotic resistance genes (ARGs) were assessed.
References
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Journal ArticleDOI
Antibiotic resistance—the need for global solutions
Ramanan Laxminarayan,Ramanan Laxminarayan,Ramanan Laxminarayan,Adriano Duse,Chand Wattal,Anita K. M. Zaidi,Heiman F. L. Wertheim,Nithima Sumpradit,Erika Vlieghe,Gabriel Levy Hara,Ian M. Gould,Herman Goossens,Christina Greko,Anthony D. So,Maryam Bigdeli,Goeran Tomson,Will Woodhouse,Eva Ombaka,Arturo Quizhpe Peralta,Farah Naz Qamar,Fatima Mir,Sam Kariuki,Zulfigar A. Bhutta,Anthony R.M. Coates,Richard Bergstrom,Gerard D. Wright,Eric D. Brown,Otto Cars +27 more
TL;DR: The global situation of antibiotic resistance, its major causes and consequences, and key areas in which action is urgently needed are described and identified.
Journal ArticleDOI
Molecular mechanisms of antibiotic resistance.
TL;DR: Recent advances in understanding of the mechanisms by which bacteria are either intrinsically resistant or acquire resistance to antibiotics are reviewed, including the prevention of access to drug targets, changes in the structure and protection of antibiotic targets and the direct modification or inactivation of antibiotics.
Journal ArticleDOI
Antibiotics and Bacterial Resistance in the 21st Century
Richard J. Fair,Yitzhak Tor +1 more
TL;DR: In this review the factors that have been linked to the waxing of bacterial resistance are addressed and profiles of bacterial species that are deemed to be particularly concerning at the present time are illustrated.
Journal ArticleDOI
Aminoglycosides: Activity and Resistance
TL;DR: Aminoglycosides are highly potent, broad-spectrum antibiotics with many desirable properties for the treatment of life-threatening infections and have a history marked by the successive introduction of a series of milestone compounds.
Journal ArticleDOI
ARG-ANNOT, a New Bioinformatic Tool To Discover Antibiotic Resistance Genes in Bacterial Genomes
Sushim K. Gupta,Babu Roshan Padmanabhan,Seydina M. Diene,Rafael López-Rojas,Marie Kempf,Luce Landraud,Jean-Marc Rolain +6 more
TL;DR: A concise database for BLAST using a Bio-Edit interface that can detect AR genetic determinants in bacterial genomes and can rapidly and easily discover putative new AR geneticeterminants is created.