Proteus mirabilis adapts to environmental change through regulation of its developmental cycle

Abstract

Every organism must adapt to environmental changes or die. The Gram-negative bacterium Proteus mirabilis adapts to a shift from a liquid to a solid environment through a process known as the swarm cycle. Alternating developmental phases of rapid outward motility with static non-motility allows P. mirabilis to grow and reach new stores of nutrients. The pathways that govern the swarm cycle in Proteus are not fully understood. In this dissertation, we sought to illuminate that gap in knowledge by determining regulatory factors critical for transition into the swarming lifestyle and through the phases of swarm development. First, we characterized how the physical environment shifts the transition between swarm phases and impacts cell morphology and growth. We then established evidence that exogenous and endogenous levels of a small molecule bias cells into specific phases of swarm development. To analyze the single-cell microscopy involved, we constructed an experimental and data processing pipeline to specifically target challenges in image analysis of P. mirabilis. Altogether, this research lays critical groundwork for untangling the regulatory controls for the swarm developmental cycle. Given the relationship between swarming and virulence, these insights could contribute to improving prevention or treatment of P. mirabilis urinary tract infections. This research could also unveil shared mechanisms in social motility with other microorganisms.