Structure of Pseudomonas aeruginosa ribosomes from an aminoglycoside-resistant clinical isolate

Yehuda Halfon, Alicia Jimenez-Fernandez, Ruggero La Rosa, Rocio Espinosa Portero, Helle Krogh Johansen, Donna Matzov, Zohar Eyal, Anat Bashan, Ella Zimmerman, Matthew Belousoff, Søren Molin, Ada Yonath

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Abstract

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.

Original languageEnglish
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number44
Pages (from-to)22275-22281
ISSN0027-8424
DOIs
Publication statusPublished - 2019

Keywords

  • Aminoglycoside
  • Antibiotic
  • Cystic fibrosis
  • Resistance
  • Ribosome

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