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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Acquisition of 16S rRNA methylase gene in Pseudomonas aeruginosa.
Keiko Yokoyama,Yohei Doi,Kunikazu Yamane,Hiroshi Kurokawa,Naohiro Shibata,Keigo Shibayama,Tetsuya Yagi,Haru Kato,Yoshichika Arakawa +8 more
TL;DR: The findings strongly suggest intergeneric lateral gene transfer of 16S rRNA methylase gene from some aminoglycoside-producing microorganisms to P aeruginosa, which could be a matter of concern in the future.
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Mycobacterial outer membranes: in search of proteins.
TL;DR: The current knowledge on the structure of the mycobacterial outer membrane and its known proteins is summarized and several hypothetical outer membrane proteins of M. tuberculosis that await discovery are highlighted.
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Exogenously acquired 16S rRNA methyltransferases found in aminoglycoside-resistant pathogenic Gram-negative bacteria: an update.
TL;DR: The worldwide dissemination of 16S-RMTases is becoming a serious global concern and this implies the necessity to continue investigations on the trend of 16 S-S rRNA methyltransferase genes to restrict their further worldwide dissemination.
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Synthesis and Spectrum of the Neoglycoside ACHN-490
James B. Aggen,Eliana Saxon Armstrong,Adam Aaron Goldblum,Paola Dozzo,Martin S. Linsell,Micah J. Gliedt,Darin Hildebrandt,Lee Ann Feeney,Aya Kubo,Rowena D. Matias,Sara Lopez,M. A. Gómez,Kenneth B. Wlasichuk,Raymond Diokno,George H. Miller,Heinz E. Moser +15 more
TL;DR: ACHN-490 was more active alone in vitro against Pseudomonas aeruginosa and Acinetobacter baumannii isolates with AG-modifying enzymes than against those with altered permeability/efflux and was advanced into clinical development as a new antibacterial agent.
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Detection of NDM-1-Producing Klebsiella pneumoniae in Kenya
TL;DR: Seven carbapenem-resistant NDM-1-positive Klebsiella pneumoniae isolates recovered from patients hospitalized between 2007 and 2009 in different wards at a referral and tertiary care center in Nairobi corresponded to the first report of N DM-1 producers in Africa.