Stochastic effects in quorum sensing mediated by extracellular vesicles*

Quorum sensing (QS) allows bacterial cells to sense changes in local cell density, and facilitates a wide array of microbial processes, including biofilm formation, regulation of virulence, and horizontal gene transfer. While, traditionally, QS was thought to be mediated solely by freely diffusing autoinducer (AI) molecules, recent experiments have shown that a substantial fraction of AI molecules are packaged in extracellular vesicles. However, the precise role of extracellular vesicles in QS is not well understood. The prevailing model of QS is based on a mean-field reaction-diffusion framework that neglects fluctuations in AI concentration. We present here a fully stochastic reaction-diffusion model of QS that accounts for fluctuations in both freely diffusing and vesicle-bound AI molecules. We find that the packaging of AI molecules in extracellular vesicles amplifies local fluctuations in AI concentration, which can dramatically decrease the QS activation time of bacterial colonies. For systems with multiple bacterial colonies, we find that extracellular vesicles provide an alternate pathway for AI transport between colonies, and may be crucial for QS in extracellular environments with a high rate of AI degradation.