Ribosome-Mediated Attenuation of vga(A) Expression Is Shaped by the Antibiotic Resistance Specificity of Vga(A) Protein Variants

Antimicrob Agents Chemother. 2020 Oct 20;64(11):e00666-20. doi: 10.1128/AAC.00666-20. Print 2020 Oct 20.

Abstract

Vga(A) protein variants confer different levels of resistance to lincosamides, streptogramin A, and pleuromutilins (LSAP) by displacing antibiotics from the ribosome. Here, we show that expression of vga(A) variants from Staphylococcus haemolyticus is regulated by cis-regulatory RNA in response to the LSAP antibiotics by the mechanism of ribosome-mediated attenuation. The specificity of induction depends on Vga(A)-mediated resistance rather than on the sequence of the riboregulator. Fine tuning between Vga(A) activity and its expression in response to the antibiotics may contribute to the selection of more potent Vga(A) variants because newly acquired mutation can be immediately phenotypically manifested.

Keywords: ABCF proteins; Staphylococcus haemolyticus; Vga(A); antibiotic resistance; clindamycin; lincosamides; pleuromutilins; regulation of gene expression; ribosome-mediated attenuation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / genetics
  • Drug Resistance, Multiple, Bacterial*
  • Lincosamides
  • Macrolides
  • Ribosomes / genetics
  • Streptogramin A*

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Lincosamides
  • Macrolides
  • Streptogramin A