SubPopulations of Shiga Toxin Producing Escherichia coli: Persistence, Resistance and Pathogenicity

实验 微生物学通常假设细菌种群是同质的， 在抵抗压力或基因表达方面。但实际上，纯 菌株培养物是异质的，其中一部分细胞存在于 休眠（持续）状态，与主状态相比， 人口的主体。此外，休眠细胞在培养期间被遗漏， 它们要么失败，要么经历延迟的生长。从进化的角度来看， 持续状态是一种“赌注对冲”，其中一部分细胞将 如果种群的生存条件变得 不利的。到目前为止，大多数与持久性有关的研究都是 关于抗生素治疗后剩余的残留群体。然而， 持久性通常在土壤等更广泛的环境中遇到， 食品系统，如高压处理食品。的 剩余种群对食品安全的重要性尚不清楚 尽管病原体再生长或增强毒力的可能性是 两种可能在拟议的研究计划中，我们将研究 滋贺毒素产生中的休眠（持续、VBNC和耐受）状态 大肠杆菌（STEC）是一类重要的临床和食源性大肠杆菌， 病原体第一次，持久状态将在 STEC和触发器，都诱导或打破休眠状态确定。 与此相关的将是来自土壤微生物群的持久性调节剂 和根际，最终控制病原体：植物相互作用。为 第一次，它将证明如何原噬菌体影响持久状态 导致噬菌体和宿主相互长期存活。的研究 持续状态将使用最先进的成像技术， 与微流体相结合，使得能够在 单细胞水平。将生成处于持久状态的单元格， 收获，以便于研究休眠在抗高 除了环境持久性之外，还存在压力和溶解性腐蚀。的影响 这项研究的潜在影响是广泛的。从学术角度 将获得对原噬菌体宿主相互作用的更深入的了解。上 应用方面，研究将提供数据，以评估食品安全风险 以环境和食物系统中的持留细胞为代表。到目前为止， 风险分析经常指定一个指定的对数减少值，以验证 干预措施（例如，巴氏灭菌）的有效性，而不考虑 剩余的幸存者。虽然存在于低水平，残留的幸存者可以在储存过程中增长或在宿主体内变得更具毒性。该研究将提供数据， 评估这些风险，并更有效地控制病原体 打破休眠状态的策略。

Experimental microbiology typically assumes bacterial populations are homogenous with respect to resistance to stress or gene expression. However, in reality pure strain cultures are heterogeneous with a proportion of cells existing in a dormant (persistent) state that have enhanced resistance compared to the main body of the population. Moreover, dormant cells are missed during culturing as they either fail or experience delayed growth. In evolutionary terms the persistent state is a kind of “bet hedging” whereby a proportion of cells will survive over extended periods should conditions for the population become adverse. To date, the majority of studies relating to persistence has been with respect to residual populations remaining after antibiotic treatment. Yet, persistence is commonly encountered in the wider environment such as soil, and food systems, such as foods treated with high pressure processing. The significance of residual populations with respect to food safety is unknown although the potential for the re-growth of pathogens or enhanced virulence are both possibilities. In the proposed research program we will look at the dormant (persistent, VBNC and tolerant) state in Shiga Toxin producing Escherichia coli (STEC) a class of significant clinical and foodborne pathogens. For the first time, the persistent state will be investigated in STEC and the triggers that both induce or break the dormant state identified. Of relevance will be the regulators of persistence derived from soil microbiota and rhizosphere that ultimately control pathogen:plant interactions. For the first time, it will be demonstrated how prophage influences the persistent state leading to mutual long term survival of phage and host. Studies of the persistent state will use state-of-the-art imaging techniques in combination with microfluidics that enable manipulation/ observation at the single cell level. Cells in the persistent state will be generated and harvested to facilitate studies on the role of dormancy in resistance to high pressure and lytic phages, in addition to environmental persistence. The impact of the research is potentially wide reaching. From an academic standpoint greater insights into prophage host interactions will be obtained. On an application side the research will provide data to assess the food safety risks represented by persister cells in the environment and food systems. To date, risk analysis has frequently designated a specified log reduction to verify the efficacy of interventions (for example, pasteurization) without taking into account residual survivors. Although present at low levels, residual survivors could grow during storage or become more virulent within the host. The research will provide data to assess such risks and moreover lead to more effective pathogen control strategies through breaking of the dormant state.