Regulatory and evolutionary roles of pseudo γ-butyrolactone receptors in antibiotic biosynthesis and resistance.

Bacteria modulate their physiological behavior by responding to various signal molecules. The signals are received by cognate receptors, which usually mediate transcriptional regulation. Streptomyces employ γ-butyrolactones (GBLs) and cognate GBL receptors (GblRs) to regulate secondary metabolism and morphological development. However, there are additional transcriptional regulators called pseudo GblR regulators, which cannot bind GBLs and are not directly associated with GBL synthase. The pseudo GblR regulators may act as transcriptional repressors and respond to antibiotic signals. They play regulatory roles in coordination of antibiotic biosynthesis by connecting the hormone feed-forward loops and the antibiotic feedback loops. As the TetR family members, they might also have evolutionary roles between the transcriptional regulators of quorum sensing and antibiotic resistance. Understanding the regulatory and evolutionary roles of the pseudo GblR family would be helpful for fine-tuning regulation of antibiotic biosynthesis and resistance.