Aminoglycosides: Perspectives on Mechanisms of Action and Resistance and Strategies to Counter Resistance

Kotra, Lakshmi P.; Haddad, Jalal; Mobashery, Shahriar

doi:10.1128/aac.44.12.3249-3256.2000

Cited by 457 publications

(337 citation statements)

References 58 publications

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“…Aminoglycoside antibiotics are known to primarily bind to the 30S ribosomal subunit, inhibiting protein synthesis (46). As a consequence, aminoglycosides have also been shown to disrupt the cell envelope leading to cell death.…”

Section: Discussionmentioning

confidence: 99%

Spatially dependent alkyl quinolone signaling responses to antibiotics in Pseudomonas aeruginosa swarms

Morales-Soto¹,

Dunham

Baig

et al. 2018

Journal of Biological Chemistry

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There is a general lack of understanding about how communities of bacteria respond to exogenous toxins such as antibiotics. Most of our understanding of community-level stress responses comes from the study of stationary biofilm communities. Although several community behaviors and production of specific biomolecules affecting biofilm development and associated behavior have been described for Pseudomonas aeruginosa and other bacteria, we have little appreciation for the production and dispersal of secreted metabolites within the 2D and 3D spaces they occupy as they colonize, spread, and grow on surfaces. Here we specifically studied the phenotypic responses and spatial variability of alkyl quinolones, including the Pseudomonas quinolone signal (PQS) and members of the alkyl hydroxyquinoline (AQNO) subclass, in P. aeruginosa plateassay swarming communities. We found that PQS production was not a universal signaling response to antibiotics as tobramycin elicited an alkyl quinolone response while carbenicillin did not. We also found that PQS and AQNO profiles in response to tobramycin were markedly distinct and influenced these swarms on different spatial scales. The distribution of alkyl quinolones varied by several orders of magnitude within the same swarm. At some tobramycin exposures, P. aeruginosa swarms produced alkyl quinolones in the range of 150 µM PQS and 400 µM AQNO that accumulated as aggregates.

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Section: Discussionmentioning

confidence: 99%

Spatially dependent alkyl quinolone signaling responses to antibiotics in Pseudomonas aeruginosa swarms

Morales-Soto¹,

Dunham

Baig

et al. 2018

Journal of Biological Chemistry

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“…This is highlighted by the finding of the rmtA, rmtB and armA genes [26,27] causing a posttranscriptional 16S rRNA methylation. Aminoglycoside resistance can also occur by point mutations in the rrs gene, encoding the 16S rRNA of the 30S subunit, or by mutations in the rpsL gene, encoding the 30S ribosomal protein S12.…”

Section: Target Site Alterationmentioning

confidence: 99%

Antimicrobial resistance in bacteria

Bockstael

Aerschot

2009

Open Medicine

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AbstractThe development of antimicrobial resistance by bacteria is inevitable and is considered as a major problem in the treatment of bacterial infections in the hospital and in the community. Despite efforts to develop new therapeutics that interact with new targets, resistance has been reported even to these agents. In this review, an overview is given of the many therapeutic possibilities that exist for treatment of bacterial infections and how bacteria become resistant to these therapeutics.

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“…However, multidrug resistance is rapidly emerging in P. aeruginosa, whose spectrum of resistance often includes aminoglycosides as well as broad-spectrum ␤-lactams and fluoroquinolones (15). The most frequently encountered molecular mechanism for aminoglycoside resistance in P. aeruginosa is the production of aminoglycoside-modifying enzymes such as plasmid-dependent acetyltransferase (AAC), adenylyltransferase (AAD), and phosphotransferase (APH) (6,17,23). Among these, production of AAC(6Ј)-II and AAD(2Љ)-I is the most common mechanism for resistance to aminoglycosides in P. aeruginosa (1), although ribosomal mutations also play some part in aminoglycoside resistance (20).…”

mentioning

confidence: 99%

Genetic Environments of the rmtA Gene in Pseudomonas aeruginosa Clinical Isolates

Yamane

Doi

Yokoyama

et al. 2004

Antimicrob Agents Chemother

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Nine Pseudomonas aeruginosa strains showing very high levels of resistance to various aminoglycosides have been isolated from clinical specimens in seven separate Japanese hospitals in five prefectures since 1997. These strains harbor the newly identified 16S rRNA methylase gene (rmtA). When an rmtA gene probe was hybridized with genomic DNAs of the nine strains digested with EcoRI, two distinct patterns were observed. The 11.1-and 15.8-kb regions containing the rmtA genes of strains AR-2 and AR-11, respectively, were sequenced and compared. In strain AR-2, a transposase gene-like sequence (sequence 1) and a probable tRNA ribosyltransferase gene (orfA) were located upstream of rmtA, and a Na ؉ /H ؉ antiporter gene-like sequence (sequence 2) was identified downstream of rmtA. This 6.2-kbp insert (the rmtA locus) was flanked by 262-bp ␥ elements. Part of the orfQ gene adjacent to an inverted repeat was found outside of the rmtA locus. In strain AR-11, the rmtA gene and sequence 2 were found, but the 5 end of the orfA gene was truncated and replaced with IS6100. An orfQ-orfI region was present on each side of the rmtA gene in strain AR-11. The G؉C content of the rmtA gene was about 55%, and since the newly identified rmtA gene may well be mediated by some mobile genetic elements such as Tn5041, further dissemination of the rmtA gene could become an actual clinical problem in the near future.

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Aminoglycosides: Perspectives on Mechanisms of Action and Resistance and Strategies to Counter Resistance

Cited by 457 publications

References 58 publications

Spatially dependent alkyl quinolone signaling responses to antibiotics in Pseudomonas aeruginosa swarms

Spatially dependent alkyl quinolone signaling responses to antibiotics in Pseudomonas aeruginosa swarms

Antimicrobial resistance in bacteria

Genetic Environments of the rmtA Gene in Pseudomonas aeruginosa Clinical Isolates

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