Biofilms are complex and highly adapted communities of microorganisms found attached to surfaces. Among the best characterized infectious multi-cellular biofilms is the oral community known as dental plaque. Streptococcus mutans resides in the oral biofilm, and is one of the main causative agents of dental caries. Streptococci are known to monitor their population density using a peptide pheromone (CSP)/two component signalling system (ComDE) in a process classically known as quorum sensing (QS). Previous work in S. mutans has implicated the QS system in genetic competence, the stress response, bacteriocin production and biofilm formation. Our objective in this work was to thoroughly characterize the transcriptional and phenotypic response to CSP in S. mutans, and determine its role in biofilm formation. We have shown that the CSP pheromone is more than simply a QS signal, and is also an inducible ‘alarmone’ capable of communicating stress in the population. We have demonstrated that elevated concentrations of CSP such as those that occur during stress trigger autolysis in a fraction of the population. Importantly, we have shown that autolysis in S. mutans occurs via a novel mechanism of action: intracellular accumulation of a self-acting bacteriocin. We have also identified and characterized the autolysis immunity protein, which is differentially regulated from the bacteriocin to allow survival at low cell density. A second regulatory system was shown to govern expression of autolysis immunity in the absence of CSP signaling, and also contribute to the oxidative stress response in the biofilm. Finally, we present evidence that autolysis is involved in the release of DNA in the biofilm, which contributes to the architecture of the extracellular matrix and may provide a mechanism for the dissemination of fitness-enhancing genes under stress. Together, our data provides a mechanistic link between phenotypes previously ascribed to the CSP pheromone in S. mutans.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/19074 |
| Date | 19 February 2010 |
| Creators | Perry, Julie |
| Contributors | Cvitkovitch, Dennis, Lévesque, Céline |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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