Structural origins of gentamicin antibiotic action

Yoshizawa, Satoko; Fourmy, Dominique; Puglisi, Joseph D.

doi:10.1093/emboj/17.22.6437

Cited by 331 publications

(273 citation statements)

References 30 publications

(52 reference statements)

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“…and Streptomyces spp. protect their 30S ribosome through methylation of its 16S rRNA at the aminoglycoside-binding A site (10,30). For example, Kgm, which was isolated from Micromonospora purpurea (28), methylates G1405, and Kam, which was isolated from Streptomyces tenjimariensis (24), methylates A1408 (2).…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…Because the aminoglycoside antibiotic gentamicin binds to the 16S ribosomal RNA on the 30S small ribosomal subunit A site of the assembled ribosome (32), it provides a convenient alternative marker of active translation. After exposure of G. obscuriglobus cells to GTTR, we observed Texas Red signal only in regions distant from the nucleoid(s) (Fig.…”

Section: Use Of Immunoelectron Microscopy and An Antibody-independentmentioning

confidence: 99%

Spatially segregated transcription and translation in cells of the endomembrane-containing bacterium Gemmata obscuriglobus

Gottshall

Seebart

Gatlin

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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The dogma of coupled transcription and translation in bacteria has been challenged by recent reports of spatial segregation of these processes within the relatively simple cellular organization of the model organisms Escherichia coli and Bacillus subtilis. The bacterial species Gemmata obscuriglobus possesses an extensive endomembrane system. The membranes generate a very convoluted intracellular architecture in which some of the cell's ribosomes appear to have less direct access to the cell's nucleoid(s) than others. This observation prompted us to test the hypothesis that a substantial proportion of G. obscuriglobus translation may be spatially segregated from transcription. Using immunofluorescence and immunoelectron microscopy, we showed that translating ribosomes are localized throughout the cell, with a quantitatively greater proportion found in regions distal to nucleoid(s). Our results extend information about the phylogenetic and morphological diversity of bacteria in which the spatial organization of transcription and translation has been studied. These findings also suggest that endomembranes may provide an obstacle to colocated transcription and translation, a role for endomembranes that has not been reported previously for a prokaryotic organism. Our studies of G. obscuriglobus may provide a useful background for consideration of the evolutionary development of eukaryotic cellular complexity and how it led to decoupled processes of gene expression in eukaryotes.

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“…21,22 Recent structural and biochemical studies have suggested a potential mechanism by which aminoglycosides achieve their antitranslational effects. 23,12,[24][25][26][27][28]13,29,14,19,30,15 According to this mechanism, A1492 and A1493 are in conformational equilibria between intrahelical and extrahelical states. When in their extrahelical states, both bases engage in interactions with minihelix formed by the mRNA codon and the tRNA anticodon.…”

Section: Greater Extents Of Aminoglycoside-induced Reduction In the Mmentioning

confidence: 99%

Use of 2-aminopurine as a fluorescent tool for characterizing antibiotic recognition of the bacterial rRNA A-site

2007

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Spectroscopic and calorimetric techniques have been employed to characterize the impact of incorporation of the fluorescent base analog 2-aminopurine into the 1492 or 1493 position of an E. coli rRNA A-site model oligonucleotide, as well as the energetics and dynamics associated with recognition of this A-site model oligomer by aminoglycoside antibiotics. The results of these studies indicate that incorporation of 2AP into either the 1492 or 1493 position does not perturb the structure or stability of the host RNA or its aminoglycoside binding affinity. In addition, the results also highlight drug-induced reduction in the mobilities of the bases at both positions 1492 and 1493 as a potentially key determinant of bactericidal potency.

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Structural origins of gentamicin antibiotic action

Cited by 331 publications

References 30 publications

Genetic Environments of the rmtA Gene in Pseudomonas aeruginosa Clinical Isolates

Genetic Environments of the rmtA Gene in Pseudomonas aeruginosa Clinical Isolates

Spatially segregated transcription and translation in cells of the endomembrane-containing bacterium Gemmata obscuriglobus

Use of 2-aminopurine as a fluorescent tool for characterizing antibiotic recognition of the bacterial rRNA A-site

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