RNA Metabolism and a New Mode of Development in Streptomyces

Abstract

Streptomyces are soil bacteria best known for their ability to produce medicinally useful compounds and for their complex life cycle. RNA processing represents a critical layer of regulatory control in bacteria, and RNA cleavage is mediated by ribonucleases (RNases). We probed the roles of RNase III and RNase J in the emerging model system Streptomyces venezuelae. We found both RNases impact the development and metabolism of S. venezuelae, and are essential for ribosome activity and assembly. While investigating the metabolic changes associated with the RNase mutants, we made a discovery that shifted the focus of my Ph.D. work. For the past 70 years, it had been thought that Streptomyces grow as static colonies. We discovered that when S. venezuelae is grown beside yeast, S. venezuelae grows in a completely novel way termed ‘exploration’. Exploring colonies can rapidly traverse surfaces. Remarkably, exploring colonies release an airborne volatile organic compound (VOC) that serves to induce exploration in physically separated streptomycetes. We identified the VOC as being trimethylamine (TMA), and discovered that this VOC induces Streptomyces exploration by raising the pH of the surrounding environment. VOCs have important roles in influencing microbial community dynamics, and we analyzed how TMA produced by exploring Streptomyces impacts other soil microbes. We found TMA inhibits the growth of other microbes by raising environmental pH and altering iron availability. Exploring Streptomyces overcome this iron deficiency by producing siderophores, and by upregulating siderophore uptake clusters. Streptomyces exploration is rapid, and we sought to identify the cellular factors driving exploration. Previous work has shown Streptomyces grow by hyphal tip extension governed by the protein DivIVA. In contrast, many rod-shaped bacteria grow using the protein MreB. We demonstrate that exploratory growth requires contributions from both DivIVA and MreB. Employing two distinct growth mechanisms in this manner is unprecedented in bacteria.