Detailed mutational analysis of Vga(A) interdomain linker: implication for antibiotic resistance specificity and mechanism

Antimicrob Agents Chemother. 2015 Feb;59(2):1360-4. doi: 10.1128/AAC.04468-14. Epub 2014 Dec 15.

Abstract

Detailed mutational analysis examines the roles of individual residues of the Vga(A) linker in determining the antibiotic resistance phenotype. It defines a narrowed region of residues 212 to 220 whose composition determines the resistance specificity to lincosamides, pleuromutilins, and/or streptogramins A. From the analogy with the recently described function of the homologous ABC-F protein EttA as a translational factor, we infer that the Vga(A) linker interacts with the ribosome and directly or indirectly affects the binding of the respective antibiotic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Cryoelectron Microscopy
  • Diterpenes / pharmacology
  • Drug Resistance, Multiple, Bacterial
  • Lincosamides / pharmacology
  • Microbial Sensitivity Tests
  • Pleuromutilins
  • Polycyclic Compounds
  • Ribosomes / metabolism
  • Streptogramins / pharmacology

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Diterpenes
  • Lincosamides
  • Polycyclic Compounds
  • Streptogramins

Associated data

  • PDB/1SM1
  • PDB/3I9C
  • PDB/3J5S
  • PDB/3OFZ