Toxin-antitoxin loci and bacterial survival in the external environment

毒素-抗毒素位点和细菌在外部环境中的存活

• 批准号: RGPIN-2014-05631
• 负责人: Levesque, Celine
• 金额: $ 2.62万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=657350
• 关键词: Toxin; antitoxin; loci; bacterial; survival

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.

生物膜代表细菌生命的主要形式。当存在有利于生长的表面或界面和条件时，细菌几乎总是组装成一组封装在自我产生的保护性细胞外基质内的细胞。生物膜允许细菌在恶劣的环境中存活，例如UV暴露、脱水、盐度和几种消毒剂和生物杀灭剂。微生物生物膜非常复杂。最令人惊讶的事实是，即使在基因相同的细胞的单物种生物膜中，表型异质性也存在。生物膜中的细胞分化可能取决于细胞周围的局部环境条件。细菌的一个基本特性是它们在面对波动的环境时调节细胞生长的能力。大多数细菌染色体含有许多毒性基因，这些基因诱导细胞亚群的可逆休眠状态。通过进入休眠状态，这些持续细胞能够在压力条件下生存。当不利条件消退时，这些休眠的坚持者复苏并重新填充生物膜。休眠表型使得固着细菌极难杀死并从生物或非生物表面移除。染色体毒素-抗毒素（TA）模块已被提出作为细胞生长的调节剂，以响应环境胁迫。TA模块由一对编码两种组分的基因组成，即稳定毒素和其同源的不稳定抗毒素。虽然毒素总是蛋白质，但抗毒素是RNA或蛋白质。在正常情况下，毒素蛋白被抗毒素抵消。TA对在细胞中形成稳定的复合物，防止在正常生长条件下的毒性。然而，当毒素和抗毒素之间的平衡被扰乱时，通常在细胞损伤或应激条件下，毒素从TA复合物释放，导致细胞生长停滞。TA系统存在于几乎所有的细菌染色体中，这证明了它们在细菌生理学中的重要性。使用口腔生物膜生物体变形链球菌作为模型-选择，因为它的相关性的生物膜的生活方式，我的总体目标是回答以下问题：微生物生长调节剂，如TA模块参与细胞生长停滞过程，有利于整个生物膜人口，从而使物种的生存在突然不利的环境变化的情况下？众所周知，微生物生物膜难以根除。我的实验室正试图通过研究TA模块作为开发成功防污策略的潜在目标来克服这一障碍。使用最先进的光学和基因组工具来阐明生物膜的生理学和基因活性，我的研究有可能有助于开发成本效益高的生物杀灭策略，以控制和根除微生物生物膜。