ENVIRONMENTAL EFFECTS ON BACTERIAL COMMUNICATION AND COMMUNAL BEHAVIOR

Abstract

Despite their autonomous nature, bacteria can often reside within complex, multicellular communities. One benefit of communal organization is the protection it offers from hazardous environments around the cells, which can come in the form of physical shielding or collective adaptive behaviors that arise from cell aggregation. This dissertation explores how environmental conditions itself might modulate or trigger these collective cell behaviors. We first explored how the environment can affect the active coordination of collective cell behavior, which involves cell-to-cell communication mechanisms such as quorum sensing (QS). Using a microfluidic platform to modulate the environment, we showed that existing explanations of environmental dependence pertaining to modulation of signal retention alone were inadequate in explaining the response. Instead, a dynamics-based analysis coupled with a mathematical model revealed a regulatory mechanism that is defined by the growth-mediated balance between synthesis and dilution of the signaling machinery proteins. This mechanism is able to account for the temporal and spatial properties observed during the onset and propagation of the collective response. These properties culminated in a cell education strategy that effectively combines response diversification with cell signaling to accelerate the onset of the collective cell behavior, which can have tremendous implications for the fitness of the cells that can exhibit this behavior. In addition, we also examined the effects of direct environmental cues, such as mechanical cues, on the emergence of collective cell behaviors. We found that physical confinement of bacterial colonies can lead to a buildup of self-imposed mechanical stress, which can elicit a biological stress response and the secretion of biofilm-related extracellular materials. We demonstrate that this renders the colony biofilm-like, with the associated functional consequence of increased antibiotic tolerance. Across these studies, we combined engineering approaches with experimentation and computational modeling to explore the relationship between bacterial colonies and its surrounding environment and found a high degree of dependence, most often reflected in spatial dependences of responses. As the appreciation for the importance of the microenvironment and its influence on bacterial colonies grow, we anticipate that the interdisciplinary approaches presented here will prove to be valuable tools in helping us understand the workings of bacterial collective cell behavior

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