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

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Halfon Y, Jimenez-Fernandez A, La Rosa R, Espinosa Portero R, Krogh Johansen H, Matzov D, Eyal Z, Bashan A, Zimmerman E, Belousoff M, Molin S, Yonath A
OpenAccess logo Proc Natl Acad Sci U S A 116 22275-22281 (2019)
Related entries: 6spb, 6spc, 6spd, 6spf, 6spg

Cited: 18 times
EuropePMC logo PMID: 31611393

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.

Articles - 6spe mentioned but not cited (1)

  1. Structure of Pseudomonas aeruginosa ribosomes from an aminoglycoside-resistant clinical isolate. Halfon Y, Jimenez-Fernandez A, La Rosa R, Espinosa Portero R, Krogh Johansen H, Matzov D, Eyal Z, Bashan A, Zimmerman E, Belousoff M, Molin S, Yonath A. Proc Natl Acad Sci U S A 116 22275-22281 (2019)


Reviews citing this publication (5)

  1. Pseudomonas aeruginosa adaptation and evolution in patients with cystic fibrosis. Rossi E, La Rosa R, Bartell JA, Marvig RL, Haagensen JAJ, Sommer LM, Molin S, Johansen HK. Nat Rev Microbiol 19 331-342 (2021)
  2. Antibiotic Combination Therapy: A Strategy to Overcome Bacterial Resistance to Aminoglycoside Antibiotics. Wang N, Luo J, Deng F, Huang Y, Zhou H. Front Pharmacol 13 839808 (2022)
  3. Aminoglycoside Resistance: Updates with a Focus on Acquired 16S Ribosomal RNA Methyltransferases. Wachino JI, Doi Y, Arakawa Y. Infect Dis Clin North Am 34 887-902 (2020)
  4. Structural Heterogeneities of the Ribosome: New Frontiers and Opportunities for Cryo-EM. Poitevin F, Kushner A, Li X, Dao Duc K. Molecules 25 E4262 (2020)
  5. Engineering the Translational Machinery for Biotechnology Applications. Wang T, Liang C, An Y, Xiao S, Xu H, Zheng M, Liu L, Wang G, Nie L. Mol Biotechnol 62 219-227 (2020)

Articles citing this publication (12)



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