Soil survival and re-emergence, the continued threat of plague

土壤生存和重新出现，鼠疫的持续威胁

• 批准号: 2746469
• 金额: --
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2746469
• 关键词: Soil; survival; re; emergence; continued

Hypothesis, Rationale and Significance.As the causative agent of plague, Yersinia pestis occupies a prominent place in human history as one of the most destructive infectious human diseases. Fleas and rats have been associated with the spread of the disease with research dating back as far as 1914 ensuring that this model of transmission has become scientific dogma. The general acceptance being that within an inveterate rodent population, enzootic plague episodes ensure Y. pestis is passed through a partially resistant host population by fleas and upon transmission into epizootic hosts plague rapidly spreads. Y. pestis is therefore circulating in associated hosts prior to re-emergence in the human population. Although the elegance of this model of transmission has endured, it is hugely oversimplified. For example, in locations where there have been no human cases or mass rodent die-offs, plague often re-emerges decades after an outbreak such as in Algeria, Libya, Madagascar and India 57, 25, 60 and 30 years later respectively. Given that Y. pestis evolved from a near identical (approx. 98% DNA identity) free-living soil borne gastrointestinal pathogen ancestor, Yersinia pseudotuberculosis, it is highly likely that apparently random plague resurgence events are actually due to the bacteria surviving under highly diverse ecological conditions by adopting a 'sit and wait' lifestyle in soil. However, soil samples used for laboratory Y. pestis survival experiments are almost always sterilized and such experiments generally assume that Y. pestis would survive independently and overlook survival strategies such as biofilm formation in soils or in association with other bacteria, fungi, protozoa or nematodes. It is already known that Y. pestis is resistant to trophozoite predation and can survive and replicate intracellularly in Dictyostelium discoideum and Acanthamoeba castellani and both Y. pestis and Y. pseudotuberculosis can also colonise the soil-dwelling nematode worm Caenorhabditis elegans, which has been exploited as an infection model for biotic surface biofilm formation.Objectives.Fundamental biological questions underlying the biology and molecular mechanisms controlling the soil-dwelling Y. pestis lifestyle have not been investigated and as a WHO classified re-emerging pathogen which is still endemic in some parts of the world, this significant gap in our understanding of plague biology is of grave concern.This PhD project therefore aims to conduct an in-depth study to understand how the soil environment, and associated amoebae and nematodes act as significant reservoirs for Y. pestis during inter-epizootic episodes by addressing the following research questions. 1. How do soil environments impact on Y. pestis survival? 2. Does the presence of nematodes and amoeba enhance Y. pestis survival in soil? 3. What are the key genes and molecular mechanisms involved in Y. pestis survival in soil? These questions will be addressed using a variety of approaches including biofilm persistence assays in soils, amoebae and nematodes infection assays along with genomic and transcriptomic studies, transposon insertion sequencing technologies and targeted gene mutations. The project will be suitable for a student who has a keen interest in molecular genetics and infectious disease and is happy to train to work under containment level 3 conditions. Recent substantial NERC funding through to 2026 means that the student will embed into a team working on complementary aspects of this project and will therefore be fully supported throughout.

鼠疫耶尔森氏菌作为鼠疫的病原体，是人类历史上最具破坏性的传染病之一，在人类历史上占有重要地位。跳蚤和老鼠与疾病的传播有关，早在1914年就有研究表明这种传播模式已成为科学教条。普遍接受的是，在一个根深蒂固的啮齿动物种群，地方性鼠疫事件确保Y。鼠疫通过跳蚤通过部分抗性宿主种群传播，一旦传播到动物流行病宿主，鼠疫迅速蔓延。Y.因此，鼠疫在重新出现于人群之前先在相关宿主中传播。尽管这种传播模式的优雅经久不衰，但它过于简单化了。例如，在没有人类病例或大规模啮齿动物死亡的地方，鼠疫往往在爆发几十年后再次出现，如阿尔及利亚、利比亚、马达加斯加和印度，分别在57年、25年、60年和30年后再次出现。如果Y。鼠疫是从一个几乎相同的（大约）98%的DNA同一性）自由生活的土壤传播的胃肠道病原体祖先，假结核耶尔森氏菌，这是很有可能的，显然是随机鼠疫死灰复燃事件实际上是由于细菌生存在高度多样化的生态条件下，通过采取'坐着等待'的生活方式在土壤中。然而，用于实验室Y.鼠疫菌的存活实验几乎总是无菌的，并且这样的实验通常假定Y.鼠疫将独立生存，而忽视了生存策略，如在土壤中形成生物膜或与其他细菌、真菌、原生动物或线虫结合。已知Y.鼠疫杆菌能抵抗滋养体的捕食，并能在盘基网柄线虫和卡氏阿米巴中存活和细胞内复制。鼠疫菌和Y. pseudotuberculosis也可以定殖的土壤中居住的线虫线虫秀丽隐杆线虫，这已被开发为生物表面生物膜formation.Objectives.fundamental生物学问题的生物学和分子机制控制的土壤中居住的Y。鼠疫菌的生活方式尚未被调查，作为世界卫生组织分类的重新出现的病原体，它仍然在世界某些地区流行，我们对鼠疫生物学的理解存在重大差距，因此，本博士项目旨在进行深入研究，以了解土壤环境，以及相关的阿米巴和线虫如何作为鼠疫菌的重要宿主。通过解决以下研究问题，对动物间流行病期间的鼠疫进行了研究。1.土壤环境对Y.鼠疫幸存者2.线虫和变形虫的存在是否会增强Y。鼠疫菌在土壤中的存活情况3. Y.鼠疫菌在土壤中的存活情况这些问题将使用各种方法来解决，包括土壤中的生物膜持久性测定，阿米巴和线虫感染测定沿着基因组和转录组学研究，转座子插入测序技术和靶向基因突变。该项目将适合对分子遗传学和传染病有浓厚兴趣的学生，并乐于接受在3级密封条件下工作的培训。最近大量的NERC资金到2026年意味着学生将嵌入到一个团队工作在这个项目的互补方面，因此将在整个过程中得到充分的支持。