Real-time measurements of aminoglycoside effects on protein synthesis in live cells
Javier Aguirre Rivera,Jimmy Larsson,Ivan L. Volkov,A. Carolin Seefeldt,Suparna Sanyal,Magnus Johansson +5 more
Reads0
Chats0
TLDR
The results suggest that the drugs slow down translation elongation two- to fourfold in general, and the number of elongation cycles per initiation event seems to decrease to the same extent, implying that none of the drugs used in this study cause severe inhibition of translocation.Abstract:
The spread of antibiotic resistance is turning many of the currently used antibiotics less effective against common infections. To address this public health challenge, it is critical to enhance our understanding of the mechanisms of action of these compounds. Aminoglycoside drugs bind the bacterial ribosome, and decades of results from in vitro biochemical and structural approaches suggest that these drugs disrupt protein synthesis by inhibiting the ribosome's translocation on the messenger RNA, as well as by inducing miscoding errors. So far, however, we have sparse information about the dynamic effects of these compounds on protein synthesis inside the cell. In the present study, we measured the effect of the aminoglycosides apramycin, gentamicin, and paromomycin on ongoing protein synthesis directly in live Escherichia coli cells by tracking the binding of dye-labeled transfer RNAs to ribosomes. Our results suggest that the drugs slow down translation elongation two- to fourfold in general, and the number of elongation cycles per initiation event seems to decrease to the same extent. Hence, our results imply that none of the drugs used in this study cause severe inhibition of translocation.read more
Citations
More filters
Journal ArticleDOI
Visualizing translation dynamics at atomic detail inside a bacterial cell
TL;DR: In this article , a high-resolution in-cell average map of all translating ribosomes and build an atomic model for the M. pneumoniae ribosome was used to visualize the structural dynamics of translation inside the bacterium Mycoplasma pneumoniae.
Journal ArticleDOI
Enhanced corrosion resistance, antibacterial activity and biocompatibility of gentamicin-montmorillonite coating on Mg alloy-in vitro and in vivo studies
Jaime Galbarro García,Lijun Fan,Wenxin Sun,Yu-Hong Zou,Qian-qian Xu,Rong-Chang Zeng,Rong-Chang Zeng,Jingrui Tian +7 more
TL;DR: In this article, a synergistic coating strategy combining montmorillonite (MMT) sustained release, adsorption of bacteria and gentamicin (GS) bactericidal is proposed to tackle infection issues.
Journal ArticleDOI
Mechanistic insights into translation inhibition by aminoglycoside antibiotic arbekacin.
TL;DR: In this article, fast kinetics were employed to reveal the molecular mechanism of action of a clinically used, new-generation, semisynthetic aminoglycoside Arbekacin (ABK).
Journal ArticleDOI
Molecular modelling, synthesis and antimicrobial evaluation of benzimidazole nucleoside mimetics.
Himani Chaurasia,Vishal K. Singh,Richa Mishra,Aditya K. Yadav,Nand K. Ram,Prashant Kumar Singh,Ramendra K. Singh +6 more
TL;DR: A series of new N-1-(β- d -ribofuranosyl) benzimidazole derivatives has been designed using in silico methods and synthesized as probable antimicrobial agents.
Journal ArticleDOI
Aminoglycoside-mimicking carbonized polymer dots for bacteremia treatment.
Yi-Ru Chiou,Chin-Jung Lin,Scott G. Harroun,Yi-Ru Chen,Lung Chang,An Tai Wu,Fu-Chieh Chang,Yang-Wei Lin,Han-Jia Lin,Anisha Anand,Binesh Unnikrishnan,Amit Nain,Chih-Ching Huang +12 more
TL;DR: The polymeric features of the CPDsMan/Arg, including cationic charges and specific groups, can be recognized as a safe and broad-spectrum biocide to lessen the reliance on antibiotics to treat systemic bacterial infections in the future.
References
More filters
Journal ArticleDOI
A Common Mechanism of Cellular Death Induced by Bactericidal Antibiotics
TL;DR: The results suggest that all three major classes of bactericidal drugs can be potentiated by targeting bacterial systems that remediate hydroxyl radical damage, including proteins involved in triggering the DNA damage response, e.g., RecA.
Journal ArticleDOI
Robust single-particle tracking in live-cell time-lapse sequences.
Khuloud Jaqaman,Dinah Loerke,Marcel Mettlen,Hirotaka Kuwata,Sergio Grinstein,Sandra L. Schmid,Gaudenz Danuser +6 more
TL;DR: This approach shows that the GTPase dynamin differentially affects the kinetics of long- and short-lived endocytic structures and that the motion of CD36 receptors along cytoskeleton-mediated linear tracks increases their aggregation probability.
Journal ArticleDOI
Functional insights from the structure of the 30S ribosomal subunit and its interactions with antibiotics
Andrew P. Carter,William M. Clemons,William M. Clemons,Ditlev E. Brodersen,Robert J. Morgan-Warren,Brian T. Wimberly,Venki Ramakrishnan +6 more
TL;DR: The functional implications of the high-resolution 30S crystal structure are described, and details of the interactions between the 30S subunit and its tRNA and mRNA ligands are inferred, which lead to a model for the role of the universally conserved 16S RNA residues A1492 and A1493 in the decoding process.
Journal ArticleDOI
Recognition of Cognate Transfer RNA by the 30S Ribosomal Subunit
James M. Ogle,Ditlev E. Brodersen,William M. Clemons,Michael J. Tarry,Andrew P. Carter,Venki Ramakrishnan +5 more
TL;DR: Crystal structures of the 30S ribosomal subunit in complex with messenger RNA and cognate transfer RNA in the A site, both in the presence and absence of the antibiotic paromomycin, have been solved at between 3.1 and 3.3 angstroms resolution.
Journal ArticleDOI
Interaction of antibiotics with functional sites in 16S ribosomal RNA
Danesh Moazed,Harry F. Noller +1 more
TL;DR: Chemical footprinting shows that several classes of antibiotics protect concise sets of highly conserved nucleotides in 16S ribosomal RNA when bound to ribosomes, having strong implications for the mechanism of action of these antibiotics and for the assignment of functions to specific structural features of 16S rRNA.