Mechanisms of resistance to aminoglycoside antibiotics: overview and perspectives
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
Citations
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Evolving medicinal chemistry strategies in antibiotic discovery
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New Broad-Spectrum Antibacterial Amphiphilic Aminoglycosides Active against Resistant Bacteria: From Neamine Derivatives to Smaller Neosamine Analogues
Louis Zimmermann,Indrajit Das,Jérôme Désiré,Guillaume Sautrey,Vinicius Barros R S,Micheline El Khoury,Marie-Paule Mingeot-Leclercq,Jean-Luc Décout +7 more
TL;DR: The synthesis and the activity against sensitive and resistant Gram-negative and/or Gram-positive bacteria of new amphiphilic 3',4'-dialkyl neamine derivatives and of their smaller analogues in the 6-aminoglucosamines (neosamine) series prepared from N-acetylglucosamine are reported on.
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Kanamycin Uptake Into Escherichia coli Is Facilitated by OmpF and OmpC Porin Channels Located in the Outer Membrane
Jayesh Arun Bafna,Eulàlia Sans-Serramitjana,Silvia Acosta-Gutierrez,Igor Bodrenko,Daniel Hörömpöli,Anne Berscheid,Heike Brötz-Oesterhelt,Mathias Winterhalter,Matteo Ceccarelli +8 more
TL;DR: In this paper, it was shown that porins contribute to the translocation of the antibiotics across the bacterial outer membrane, despite decades of therapeutic application of aminoglycosides.
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Repurposing Zidovudine in combination with Tigecycline for treating carbapenem-resistant Enterobacteriaceae infections.
Siew Mei Samantha Ng,J. S. P. Sioson,J. M. Yap,Fui Mee Ng,H. S. V. Ching,Jeanette W. P. Teo,Roland Jureen,Jeffrey Hill,Cheng San Brian Chia +8 more
TL;DR: Zidovudine was shown to be the most promising candidate for use in combination with Tigecycline to treat systemic CRE infections, and should involve the use of animal infection models.
Journal ArticleDOI
How kanamycin A interacts with bacterial and mammalian mimetic membranes.
TL;DR: Investigation of the initial, first key interactions of kanamycin A, as a representative aminoglycoside, with both bacterial and mammalian lipid bilayers at the molecular level indicates the bacterial membrane disruption observed by previous studies.
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.