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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.

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Ribosome-Targeting Antibiotics: Modes of Action, Mechanisms of Resistance, and Implications for Drug Design.

TL;DR: The modes of action of many ribosome-targeting antibiotics are described, the major resistance mechanisms developed by pathogenic bacteria are highlighted, and recent advances in structure-assisted design of new molecules are discussed.
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Antibiotic Resistance and the MRSA Problem

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References
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Adaptive Resistance to the “Last Hope” Antibiotics Polymyxin B and Colistin in Pseudomonas aeruginosa Is Mediated by the Novel Two-Component Regulatory System ParR-ParS

TL;DR: The identification and characterization of a novel P. aeruginosa two-component regulator affecting polymyxin-adaptive resistance, ParR-ParS (PA1799-PA1798), which was required for activation of the arnBCADTEF LPS modification operon in the presence of subinhibitory concentrations of polymyXin, colistin, or the bovine peptide indolicidin, leading to increased resistance to various polycationic
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Copper resistance is essential for virulence of Mycobacterium tuberculosis

TL;DR: Evidence is provided that Cu is used by the mammalian host to control Mtb infection and that Cu resistance mechanisms are crucial for Mtb virulence, revealing an Achilles heel of Mtb that might be a promising target for tuberculosis chemotherapy.
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Overexpression of the chromosomally encoded aminoglycoside acetyltransferase eis confers kanamycin resistance in Mycobacterium tuberculosis

TL;DR: Results have important clinical implications in that clinical isolates determined to be resistant to kanamycin may not be cross-resistant to amikacin, as is often assumed.
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Role of mycobacterial efflux transporters in drug resistance: an unresolved question

TL;DR: This review highlights recent advances in the understanding of efflux-mediated drug resistance in mycobacteria, including the distribution of Efflux systems in these organisms, their substrate profiles and their contribution to drug resistance.
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Molecular analysis of cross-resistance to capreomycin, kanamycin, amikacin, and viomycin in Mycobacterium tuberculosis

TL;DR: The data implicate rrs mutations as a molecular basis for resistance to each of the four drugs, and the genotypic and phenotypic differences seen in the development of cross-resistance when M. tuberculosis bacteria were exposed to one or two drugs have implications for selection of treatment regimens.
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