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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Journal ArticleDOI
Domain-domain interactions in the aminoglycoside antibiotic resistance enzyme AAC(6')-APH(2'').
TL;DR: Domain-domain interactions in AAC(6')-APH(2' ') offer a unique target for inhibitor strategies, as it is shown that their disruption simultaneously inhibits both activities >90%.
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Determinants of intrinsic aminoglycoside resistance in Pseudomonas aeruginosa.
Thomas Krahn,Christie Gilmour,Justin Tilak,Sebastien Fraud,Nicholas Kerr,Calvin Ho-Fung Lau,Keith Poole +6 more
TL;DR: Screening of a transposon insertion mutant library of Pseudomonas aeruginosa for increased susceptibility to paromomycin identified a number of genes whose disruption enhanced susceptibility of this organism to multiple aminoglycosides, including tobramycin, amikacin, and gentamicin.
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Identification and characterization of inhibitors of the aminoglycoside resistance acetyltransferase Eis from Mycobacterium tuberculosis.
TL;DR: The continuous emergence and global spread of multidrug-resistant and extensively drug-resistant strains of Mycobacterium tuberculosis, the causative agent of TB, underscore the pressing clinical need for novel treatments of this deadly infectious disease and for new solutions to alleviate the resistance problem.
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Can Plazomicin Alone or in Combination Be a Therapeutic Option against Carbapenem-Resistant Acinetobacter baumannii?
TL;DR: Findings indicate the potential utility of plazomicin in combination with other antibiotics (mainly carbapenems) for the treatment of A. baumannii infections, including those caused bycarbapenem-resistant isolates.
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MexY-Promoted Aminoglycoside Resistance in Pseudomonas aeruginosa: Involvement of a Putative Proximal Binding Pocket in Aminoglycoside Recognition
TL;DR: The results presented here indicate that aminoglycosides are likely not captured and exported by this RND pump component in a unique manner but rather utilize a previously defined export pathway that involves a proximal drug-binding pocket that is also implicated in the export of nonaminogly cosides.