Journal article
Structure of Pseudomonas aeruginosa ribosomes from an aminoglycoside-resistant clinical isolate
Weizmann Institute of Science1
Infection Microbiology, Research Groups, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark2
Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark3
Research Groups, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark4
University of Copenhagen5
Monash University6
Resistance to antibiotics has become a major threat to modern medicine. The ribosome plays a fundamental role in cell vitality by the translation of the genetic code into proteins; hence, it is a major target for clinically useful antibiotics. We report here the cryo-electron microscopy structures of the ribosome of a pathogenic aminoglycoside (AG)-resistant Pseudomonas aeruginosa strain, as well as of a nonresistance strain isolated from a cystic fibrosis patient.
The structural studies disclosed defective ribosome complex formation due to a conformational change of rRNA helix H69, an essential intersubunit bridge, and a secondary binding site of the AGs. In addition, a stable conformation of nucleotides A1486 and A1487, pointing into helix h44, is created compared to a non-AG-bound ribosome.
We suggest that altering the conformations of ribosomal protein uL6 and rRNA helix H69, which interact with initiation-factor IF2, interferes with proper protein synthesis initiation.
Language: | English |
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Publisher: | National Academy of Sciences |
Year: | 2019 |
Pages: | 22275-22281 |
ISSN: | 10916490 and 00278424 |
Types: | Journal article |
DOI: | 10.1073/pnas.1909831116 |
ORCIDs: | Rosa, Ruggero La , 0000-0003-0268-3717 and Molin, Søren |