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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)
Related entries: 6spb, 6spc, 6spd, 6spe, 6spf

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 - 6spg mentioned but not cited (4)

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  4. 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 (4)

  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. 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)
  3. 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)
  4. 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)

Articles citing this publication (10)

  1. Compensatory evolution of Pseudomonas aeruginosa's slow growth phenotype suggests mechanisms of adaptation in cystic fibrosis. La Rosa R, Rossi E, Feist AM, Johansen HK, Molin S. Nat Commun 12 3186 (2021)
  2. The many antibiotic resistance and tolerance strategies of Pseudomonas aeruginosa. Sindeldecker D, Stoodley P. Biofilm 3 100056 (2021)
  3. SEVAtile: a standardised DNA assembly method optimised for Pseudomonas. Lammens EM, Boon M, Grimon D, Briers Y, Lavigne R. Microb Biotechnol 15 370-386 (2022)
  4. Safe and easy in vitro evaluation of tmRNA-SmpB-mediated trans-translation from ESKAPE pathogenic bacteria. Thépaut M, Campos-Silva R, Renard E, Barloy-Hubler F, Ennifar E, Boujard D, Gillet R. RNA 27 1390-1399 (2021)
  5. Structure of the 70S Ribosome from the Human Pathogen Acinetobacter baumannii in Complex with Clinically Relevant Antibiotics. Nicholson D, Edwards TA, O'Neill AJ, Ranson NA. Structure 28 1087-1100.e3 (2020)
  6. Cryo-electron Microscopy Structure of the Acinetobacter baumannii 70S Ribosome and Implications for New Antibiotic Development. Morgan CE, Huang W, Rudin SD, Taylor DJ, Kirby JE, Bonomo RA, Yu EW. mBio 11 (2020)
  7. Finding priority bacterial ribosomes for future structural and antimicrobial research based upon global RNA and protein sequence analysis. Cooper HB, Krause KL, Gardner PP. PeerJ 11 e14969 (2023)
  8. Maturation of 23S rRNA includes removal of helix H1 in many bacteria. Shatoff EA, Gemler BT, Bundschuh R, Fredrick K. RNA Biol 18 856-865 (2021)
  9. SARS-CoV-2 Membrane Protein: From Genomic Data to Structural New Insights. Marques-Pereira C, Pires MN, Gouveia RP, Pereira NN, Caniceiro AB, Rosário-Ferreira N, Moreira IS. Int J Mol Sci 23 2986 (2022)
  10. Structural basis of sequestration of the anti-Shine-Dalgarno sequence in the Bacteroidetes ribosome. Jha V, Roy B, Jahagirdar D, McNutt ZA, Shatoff EA, Boleratz BL, Watkins DE, Bundschuh R, Basu K, Ortega J, Fredrick K. Nucleic Acids Res 49 547-567 (2021)


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