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: 2014
• 资助国家: 加拿大
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=567289
• 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.

生物膜是细菌生命的主要形式。当有一个表面或界面，以及有利于生长的条件时，细菌几乎总是会聚集成一组细胞，包裹在自己产生的保护性细胞外基质中。生物膜允许细菌在恶劣的环境中生存，如紫外线照射、脱水、盐度以及几种消毒剂和杀生剂。微生物生物膜是非常复杂的。最令人惊讶的事实是，即使在由遗传相同的细胞组成的单一物种生物膜中，也存在表型异质性。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。细菌的一个基本属性是它们在面对波动的环境时调节细胞生长的能力。大多数细菌染色体都含有许多有毒基因，这些基因会导致一群细胞处于可逆的休眠状态。通过进入休眠状态，这些持久细胞能够在压力条件下生存下来。当不利条件消退时，这些休眠的持久者复苏并重新滋生生物膜。休眠表型使固着细菌极难从生物或非生物表面杀死和移除。染色体毒素-抗毒素(TA)模块被认为是细胞在应对环境胁迫时的生长调节因子。TA模块由一对基因组成，编码两种成分，一种是稳定毒素，另一种是同源不稳定抗毒素。虽然毒素总是蛋白质，但抗毒素要么是RNA，要么是蛋白质。在正常情况下，毒素蛋白会被抗毒素所抵消。TA对在细胞内形成稳定的复合体，在正常生长条件下防止毒性。然而，当毒素和抗毒素之间的平衡被破坏时，通常是在细胞损伤或应激条件下，毒素从TA复合体中释放出来，导致细胞生长停滞。TA系统在几乎所有的细菌染色体中都存在，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变形链球菌作为模型-选择它是因为它与生物膜生活方式相关，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，是否参与细胞生长抑制过程，从而使整个生物膜种群受益，从而使物种在突然不利的环境变化时得以生存？微生物生物膜是出了名的难以根除。我的实验室正试图通过研究TA模块来克服这一障碍，以此作为开发成功的防污染策略的潜在目标。使用最先进的光学和基因组工具来阐明生物膜的生理和基因活性，我的研究有可能有助于开发具有成本效益的生物杀灭策略，以控制和根除微生物生物膜。