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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References
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6′′‐Thioether Tobramycin Analogues: Towards Selective Targeting of Bacterial Membranes
Ido M. Herzog,Keith D. Green,Yifat Berkov-Zrihen,Mark Feldman,Roee R. Vidavski,Anat Eldar-Boock,Ronit Satchi-Fainaro,Avigdor Eldar,Sylvie Garneau-Tsodikova,Micha Fridman +9 more
TL;DR: Three modes of action lead to bacterial resistance to AGs: reduction in the intracellular concentration of the antibiotics by efflux pump proteins or through reduced membrane permeability; structural modifications of the 16S ribosomal RNA leading to reduced target affinity; and deactivation by AG-modifying enzymes (AMEs).
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Sequence of Conjugative Plasmid pIP1206 Mediating Resistance to Aminoglycosides by 16S rRNA Methylation and to Hydrophilic Fluoroquinolones by Efflux
Bruno Périchon,Pierre Bogaerts,Thierry Lambert,Lionel Frangeul,Patrice Courvalin,Marc Galimand +5 more
TL;DR: Self-transferable IncFI plasmid pIP1206 carries two new resistance determinants: qepA, which confers resistance to hydrophylic fluoroquinolones by efflux, and rmtB, which specifies a 16S rRNA methylase conferring high-level aminoglycoside resistance.
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The SmeYZ Efflux Pump of Stenotrophomonas maltophilia Contributes to Drug Resistance, Virulence-Related Characteristics, and Virulence in Mice
TL;DR: Findings suggest the possibility of attenuation of the resistance and virulence of S. maltophilia with inhibitors of the SmeYZ efflux pump.
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Involvement of an ATP-dependent protease (PA0779/AsrA) in inducing heat shock in response to tobramycin in Pseudomonas aeruginosa
TL;DR: The results of this work suggest that the tobramycin concentration has a significant impact on the gene expression of P. aeruginosa, with lethal concentrations resulting in immediate adaptations conferring short-term protection, such as the induction of the heat shock response, and with subinhibitory concentrations leading to more sustainable long- term protection mechanisms, suchAs increased efflux.
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Neisseria gonorrhoeae strain with high-level resistance to spectinomycin due to a novel resistance mechanism (mutated ribosomal protein S5) verified in Norway
Magnus Unemo,Daniel Golparian,Vegard Skogen,Vegard Skogen,Anne O. Olsen,Anne O. Olsen,Harald Moi,Harald Moi,Gaute Syversen,Stig Ove Hjelmevoll +9 more
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