Osmotic stress responses and the biology of the second messenger c-di-AMP in Streptomyces

Streptomyces are prolific antibiotic producers that thrive in soil, where they encounter diverse environmental cues, including osmotic challenges caused by rainfall and drought. Despite their enormous value in the biotechnology sector, which often relies on ideal growth conditions, how Streptomyces react and adapt to osmotic stress is heavily understudied. This is likely due to their complex developmental biology and an exceptionally broad number of signal transduction systems. With this review, we provide an overview of Streptomyces' responses to osmotic stress signals and draw attention to open questions in this research area. We discuss putative osmolyte transport systems that are likely involved in ion balance control and osmoadaptation and the role of alternative sigma factors and two-component systems (TCS) in osmoregulation. Finally, we highlight the current view on the role of the second messenger c-di-AMP in cell differentiation and the osmotic stress responses with specific emphasis on the two models, S. coelicolor and S. venezuelae.