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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Yazeed A. Al Sheikh,Mohammed Ali M. Marie,James John,James John,Lakshmana Gowda Krishnappa,Khaled Homoud M. Dabwab +5 more
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blaKPC and rmtB on a single plasmid in Enterobacter amnigenus and Klebsiella pneumoniae isolates from the same patient
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Identification of a Novel 6′-N-Aminoglycoside Acetyltransferase, AAC(6′)-Iak, from a Multidrug-Resistant Clinical Isolate of Stenotrophomonas maltophilia
Tatsuya Tada,Tohru Miyoshi-Akiyama,Rajan K. Dahal,Shyam Kumar Mishra,Kayo Shimada,Hiroshi Ohara,Teruo Kirikae,Bharat Mani Pokhrel +7 more
TL;DR: Stenotrophomonas maltophilia IOMTU250 has a novel 6′-N-aminoglycoside acetyltransferase-encoding gene, aac(6′)-Iak, which shows decreased susceptibility to arbekacin, dibekacIn, neomycin, netilmicin, sisomicin, and tobramycin but not apramYcin, gentamicin, or lividomycin.
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Outbreak of Serratia marcescens Coproducing ArmA and CTX-M-15 Mediated High Levels of Resistance to Aminoglycoside and Extended-Spectrum Beta-Lactamases, Algeria
Rima Batah,Lotfi Loucif,Lotfi Loucif,Abiola Olumuyiwa Olaitan,Nafissa Boutefnouchet,Hamoudi Allag,Jean-Marc Rolain +6 more
TL;DR: The co-occurrence of armA methyltransferase with ESBL in S. marcescens clinical isolates in Eastern Algeria is reported for the first time, likely suggesting an outbreak of such isolate in the urology unit.
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A random sequential mechanism of aminoglycoside acetylation by Mycobacterium tuberculosis Eis protein.
TL;DR: A systematic analysis of steady-state kinetics of acetylation of kanamycin A and neomycin B by Eis as a function of concentrations of these aminoglycosides and the acetyl donor, acetyl coenzyme A, reveals that MtEis employs a random-sequential bisubstrate mechanism ofacetylation and yields the values of the kinetic parameters of this mechanism.