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
Ribosome-targeting antibiotics and mechanisms of bacterial resistance
TL;DR: The recent structural insights into the mechanism of action of ribosome-targeting antibiotics and the molecular mechanisms of bacterial resistance are discussed, in addition to the approaches that are being pursued for the production of improved drugs that inhibit bacterial protein synthesis.
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Bacterial biofilm development as a multicellular adaptation: antibiotic resistance and new therapeutic strategies.
TL;DR: Novel strategies that specifically target the biofilm mode of growth have been recently described, thus providing the basis for future anti-biofilm therapy.
Journal ArticleDOI
Adaptive and Mutational Resistance: Role of Porins and Efflux Pumps in Drug Resistance
TL;DR: It is explained how adaptive and mutational events can dramatically influence the outcome of antibiotic therapy by altering the mechanisms of influx and efflux of antibiotics, which are regarded as key phenomena in the global rise of antibiotic resistance among pathogenic microorganisms.
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Broad-specificity efflux pumps and their role in multidrug resistance of Gram-negative bacteria
Hiroshi Nikaido,Jean-Marie Pagès +1 more
TL;DR: The recent investigation on the efflux pump AcrB at its structural and physiological levels, including the identification of drug affinity sites and kinetic parameters for various antibiotics, may pave the way towards the rational development of an improved new generation of antibacterial agents as well as efflux inhibitors in order to efficiently combat efflux-based resistance mechanisms.
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Mycobacterial cell wall: Structure and role in natural resistance to antibiotics
Vincent Jarlier,Hiroshi Nikaido +1 more
TL;DR: The cell wall barrier alone cannot produce significant levels of drug resistance, which requires synergistic contribution from a second factor, such as the enzymatic inactivation of drugs.