Exploring new growth modes and developmental trajectories for Streptomyces bacteria

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Streptomyces are soil bacteria with a complex, multicellular life cycle. Classical Streptomyces development involves first growing as vegetative hyphae, then raising aerial hyphae and forming spore chains. Notably, classically-growing colonies are rooted in place, with spore dispersal being the only way of colonizing new environments. We recently discovered a new Streptomyces behaviour, termed `exploration'. Exploring cultures spread rapidly over surfaces, expanding at a rate >10 times faster than classically growing cultures. We found that exploration occurs in response to nutrient depletion and is profoundly impacted by other organisms. Our recent work is, however, suggesting that there are multiple ways by which exploration can occur. Having discovered this phenomenon and pioneered the investigations into this new bacterial growth mode, we are ideally positioned to probe the mechanisms driving exploration, and the interactions affecting both exploring Streptomyces and other organisms in the soil. OBJECTIVE 1: Define the regulatory pathways governing exploration. We have determined that there are at least three pathways by which exploration can proceed, and have identified regulatory genes specifically controlling exploration via each of the three pathways. We aim to map the regulatory cascades governing exploration and determine the genes and regulatory/metabolic pathways that drive exploration. OBJECTIVE 2: Establish the mechanistic basis for rapid growth and colony expansion. How exploring Streptomyces achieve such remarkable colony expansion is entirely unknown. We have strong preliminary evidence suggesting it involves an unprecedented reprogramming of cell wall biosynthesis. We will probe the structure and composition of the cell wall during exploration, follow the localization of key cell wall biosynthetic enzymes during exploration, and determine the nature of the cell wall biosynthetic machinery required for exploration. OBJECTIVE 3: Probe the environmental and ecological implications of exploration. Streptomyces are ubiquitous soil-dwelling microbes, and exploration has the potential to bring them in close contact with other organisms in the soil.  We will assess the reciprocal effects of bacteria, fungi, phage, insects and plants on exploration. We will further examine exploration in artificial soil and soil microcosms to determine the potential for exploration in the environment. The long term goal of this research program is to understand the factors that influence bacterial growth and developmental strategies, and how these impact the ecology of these organisms. This work will provide fundamental insights into the biology of Streptomyces, and has the capacity to develop new paradigms for bacterial growth and cell wall synthesis. Our findings are further laying the foundation for strategies aimed at manipulating Streptomyces growth and interactions for the purposes of agricultural innovation or bioremediation.