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

Abstract

Vga(A) protein variants confer different levels of resistance to lincosamides, streptogramin A, and pleuromutilins (LS_AP) by displacing antibiotics from the ribosome. Here, we show that expression of <i>vga</i>(A) variants from <i>Staphylococcus haemolyticus</i> is regulated by <i>cis</i>-regulatory RNA in response to the LS_AP 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.