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
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References
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Journal ArticleDOI
Synthesis and evaluation of hetero- and homodimers of ribosome-targeting antibiotics: antimicrobial activity, in vitro inhibition of translation, and drug resistance.
Yifat Berkov-Zrihen,Keith D. Green,Kristin J. Labby,Mark Feldman,Sylvie Garneau-Tsodikova,Micha Fridman +5 more
TL;DR: This study demonstrates that covalently linking two identical or different ribosome-targeting antibiotics may lead to a broader spectrum of antimicrobial activity, improved inhibition of bacterial translation properties compared to that of the parent antibiotics, and reduction in the efficacy of some drug-modifying enzymes that confer high levels of resistance to the parent antibiotic from which the dimers were derived.
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Multidrug-resistant Providencia isolates carrying blaPER-1, blaVIM-2, and armA.
TL;DR: During May to July 2004, three strains of Providencia spp.
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ArmA Methyltransferase in a Monophasic Salmonella enterica Isolate from Food
Sophie A. Granier,Laura Hidalgo,Alvaro San Millan,Jose Antonio Escudero,Belen Gutierrez,Anne Brisabois,Bruno Gonzalez-Zorn +6 more
TL;DR: This is the first report of ArmA methyltransferase in food, showing a novel route of transmission for this resistance determinant and further surveillance in food-borne bacteria will be crucial to determine the role of food in the spread of 16S rRNA methyl transferase genes worldwide.
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Outbreak of an armA methyltransferase-producing ST39 Klebsiella pneumoniae clone in a pediatric Algerian Hospital.
TL;DR: The emergence of multidrug-resistant clones, which were likely responsible for a nosocomial outbreak, is worrying because there are already limited options in those critical situations and surveillance should be implemented to monitor the risk of emergence and spread of carbapenemases in Algeria.
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Novel Aminoglycoside 2″-Phosphotransferase Identified in a Gram-Negative Pathogen
TL;DR: Steady-state kinetic studies demonstrated that GTP, and not ATP, is the preferred cosubstrate for APH(2″)-If, which confers resistance to the 4,6-disubstituted aminoglycosides kanamycin, tobramycin, dibekacin, gentamicin, and sisomicin.