Toxin-antitoxin loci and bacterial survival in the external environment

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Biofilms represent the predominant form of bacterial life. When presented with a surface or an interface and conditions advantageous for growth, bacteria almost always will assemble as a group of cells encapsulated within a self-produced protective extracellular matrix. Biofilms allow survival of bacteria in hostile environments, such as UV exposure, dehydration, salinity, and several disinfectants and biocidal agents. Microbial biofilms are very complex. The most amazing fact is that even in a mono-species biofilm of genetically identical cells, phenotypic heterogeneity exists. Cell differentiation in biofilms may depend on the local environmental conditions surrounding the cells. A fundamental property of bacteria is their ability to regulate cell growth when faced with a fluctuating environment. Most bacterial chromosomes contain a number of toxic genes that induce a reversible state of dormancy of a subpopulation of cells. By entering into a dormant state, these persister cells are able to survive stress conditions. When the unfavourable conditions subside, these dormant persisters resuscitate and repopulate the biofilms. The dormancy phenotype makes sessile bacteria extremely difficult to kill and remove from biotic or abiotic surfaces. Chromosomal toxin-antitoxin (TA) modules have been proposed to function as regulators of cell growth in response to environmental stress. TA modules consist of a pair of genes that encode two components, a stable toxin and its cognate labile antitoxin. While toxins are always proteins, antitoxins are either RNA or proteins. Under normal circumstances, the toxin protein is counteracted by the antitoxin. TA pairs form a stabilized complex in the cell preventing toxicity under normal growth conditions. However, when the balance between the toxin and antitoxin is perturbed, usually following cellular damage or stressful conditions, the toxin is released from the TA complex leading to cell growth arrest. TA systems are found in nearly all bacterial chromosomes, which attest to their importance in bacterial physiology. Using the oral biofilm organism Streptococcus mutans as a model – chosen because of its relevance of a biofilm lifestyle, my overall goal is to answer the following question: Do microbial growth modulators such as TA modules participate in cell growth arrest processes that benefit the whole biofilm population and thereby enable survival of the species in the event of a sudden unfavourable environmental change? Microbial biofilms are notoriously difficult to eradicate. My lab is attempting to overcome this barrier by investigating TA modules as potential target for the development of successful anti-fouling strategies. Using the state-of-the art optical and genomic tools to elucidate the physiology and gene activities of biofilms, my research has the potential to contribute to the development of cost-effective biocidal strategies for the control and eradication of microbial biofilms.