Contributed by Ada Yonath, September 4, 2019 (sent for review June 10, 2019; reviewed by Alexander S. Mankin and Huang Ziwei)The cryo-electron microscopy high-resolution structures of the wild-type ribosome of the human pathogen Resistance to antibiotics has become a major threat to modern medicine. At present there are strong indications that Pseudomonas aeruginosa exhibits an epidemic population structure; clinical isolates are indistinguishable from environmental isolates, and they do not exhibit a specific (disease) habitat selection. IF2 (At the interaction site between IF2 (in red) and uL6 (The overlay of the IF2 structure on the PAuL6m ribosome suggests that H69 of the PAuL6m may clash with IF2 (Interestingly, the AG binding site is located 50 Å distant from the uL6 protein, suggesting that antibiotic resistance can also be acquired by altering the complex structure of the ribosome, affecting its interaction with central auxiliary proteins and that the mechanistic understanding of changes in the overall ribosomal structure may play a key role in mitigating antibiotic resistance. We do not capture any email address.Copyright © 2020 National Academy of Sciences. This work was also supported by iNEXT: Infrastructure for NMR, EM and X-Rays for Translational Research Project 653706, funded by the European Union Horizon 2020 program. Previous structural studies have indicated that the ribosome distinguishes between cognate and near-cognate tRNAs by monitoring the geometry of the codon–anticodon interactions of the universally conserved 16S ribosomal RNA bases G530, A1492, and A1493 in the decoding center (We suggest that a distorted IF2 binding is the link between the deletion mutation in the uL6m rProtein and the H69–h44 B2a bridge. The specific differences found between the PA native and mutant ribosomes.
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In a biofilm, the extracellular polymeric substance (EPS) causes an inhibited penetration of antibacterial agents, leading to a 100–1000 times tolerance of the bacteria. This site needs JavaScript to work properly. Sequencing of complete genomes or blocks of the accessory genome has revealed that the genome encodes a large repertoire of transporters, transcriptional regulators, and two-component regulatory systems which reflects its metabolic … This work was supported by European Research Council Grant 322581 (Novel Insights into Multi-Drug Resistance to Antibiotics and the Primordial Ribosome); the Kimmelman Center for Macromolecular Assemblies; Danish Council for Independent Research Grant Rammebevilling DFF-4181-00115; and the Novo Nordisk Foundation. We report here the cryo-electron microscopy structures of the ribosome of a pathogenic aminoglycoside (AG)-resistant … In addition, the 2 universally conserved nucleotides A1486 and A1487 (Accurate tRNA selection by the ribosome is essential for the synthesis of functional proteins. wrote the paper.Reviewers: A.S.M., University of Illinois at Chicago; and H.Z., School of Medicine, University of California San Diego.Data deposition: Atomic coordinates and EM maps for the reported EM structures have been deposited in the Protein Data Bank, This article contains supporting information online at Thank you for your interest in spreading the word on PNAS.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We determined and compared the structures of intact ribosomes purified from the native (PAnat) and the uL6 mutant (PAuL6m) clinical isolates (Comparing the structure of PAnat ribosome to other known ribosome structures revealed certain unique PA ribosome structural features.