6s13 Citations

Exit tunnel modulation as resistance mechanism of S. aureus erythromycin resistant mutant.

OpenAccess logo Sci Rep 9 11460 (2019)
Related entries: 6s0x, 6s0z, 6s12

Cited: 26 times
EuropePMC logo PMID: 31391518

Abstract

The clinical use of the antibiotic erythromycin (ery) is hampered owing to the spread of resistance genes that are mostly mutating rRNA around the ery binding site at the entrance to the protein exit tunnel. Additional effective resistance mechanisms include deletion or insertion mutations in ribosomal protein uL22, which lead to alterations of the exit tunnel shape, located 16 Å away from the drug's binding site. We determined the cryo-EM structures of the Staphylococcus aureus 70S ribosome, and its ery bound complex with a two amino acid deletion mutation in its ß hairpin loop, which grants the bacteria resistance to ery. The structures reveal that, although the binding of ery is stable, the movement of the flexible shorter uL22 loop towards the tunnel wall creates a wider path for nascent proteins, thus enabling bypass of the barrier formed by the drug. Moreover, upon drug binding, the tunnel widens further.

Articles - 6s13 mentioned but not cited (2)

  1. Exit tunnel modulation as resistance mechanism of S. aureus erythromycin resistant mutant. Halfon Y, Matzov D, Eyal Z, Bashan A, Zimmerman E, Kjeldgaard J, Ingmer H, Yonath A. Sci Rep 9 11460 (2019)
  2. Synthetic macrolides overcoming MLSBK-resistant pathogens. Ma CX, Li Y, Liu WT, Li Y, Zhao F, Lian XT, Ding J, Liu SM, Liu XP, Fan BZ, Liu LY, Xue F, Li J, Zhang JR, Xue Z, Pei XT, Lin JZ, Liang JH. Cell Discov 10 75 (2024)


Reviews citing this publication (5)

  1. Mitochondria and Antibiotics: For Good or for Evil? Suárez-Rivero JM, Pastor-Maldonado CJ, Povea-Cabello S, Álvarez-Córdoba M, Villalón-García I, Talaverón-Rey M, Suárez-Carrillo A, Munuera-Cabeza M, Sánchez-Alcázar JA. Biomolecules 11 1050 (2021)
  2. 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)
  3. RNA Modifications in Pathogenic Bacteria: Impact on Host Adaptation and Virulence. Antoine L, Bahena-Ceron R, Devi Bunwaree H, Gobry M, Loegler V, Romby P, Marzi S. Genes (Basel) 12 1125 (2021)
  4. Frozen in time: analyzing molecular dynamics with time-resolved cryo-EM. Amann SJ, Keihsler D, Bodrug T, Brown NG, Haselbach D. Structure 31 4-19 (2023)
  5. Advanced Methods for Studying Structure and Interactions of Macrolide Antibiotics. Jednačak T, Mikulandra I, Novak P. Int J Mol Sci 21 E7799 (2020)

Articles citing this publication (19)