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: NE/W003449/1
• 负责人: Joseph Bailey
• 金额: $ 5.82万
• 依托单位: York St John University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=NE%2FW003449%2F1
• 关键词: Soil; survival; re; emergence; continued

Yersinia pestis (Y. pestis) the bacterium responsible for plague, is probably the most devastating infectious diseases known to humanity and may be responsible for more human deaths than any other micro-organism in history (e.g. during the Black Death). Its 'success' is attributed to the fact that it is extremely contagious, and when untreated, death normally occurs in 1-2 days from bubonic, pneumonic or septicaemic plague. Rodents, fleas and person to person pneumonic transmission are generally considered as fundamental to its rapid spread and although elegant, several facts are inconsistent with this hugely oversimplified model. For example, it is clear that plague can vanish from an epidemic area, only to undergo a resurgence, months or often decades after the original outbreak ceased. Where plague resides during these periods of absence from host and vector populations, and what causes it to re-emerge, has not been studied in detail. Some Y. pestis strains have now acquired multi-antibiotic resistance and an upsurge in transmission of these strains would pose a severe risk to human health, so we need to understand the conditions that might cause a significant re-emergence event to occur.Y. pestis evolved from a near identical, free-living soil-borne ancestor, Yersinia pseudotuberculosis, and soil is therefore thought to be a reservoir for Y. pestis, but how it survives in, and then spreads from this environment has not been adequately investigated. Y. pestis may be protected during this soil stage of its life cycle by embedding in a self-derived protective 'slime' layer (biofilm) enabling the bacterial cells to form a protected association with other bacteria, amoebae or nematodes in the soil. In this study we focus on soil as the important environmental reservoir in which Y. pestis adopts a 'sit and wait' survival lifestyle from where it can re-enter the rodent/human population when conditions are favorable. We aim to identify the environmental and biological triggers that underpin plague survival in, and re-emergence from, soil. To do this we need to take a wide view of the soil environment including factors such as microclimate, soil type, and land cover in association with testing the impact of nematode worms and amoebae on plague survival. Our work will plug a significant and potentially dangerous gap in our understanding of plague ecology, especially important given that the World Health Organization has recently classified Y. pestis as a re-emerging zoonotic pathogen.Using Madagascar as our case study, due to its well recorded plague outbreak history, we will address this knowledge gap using a wide range of scientific approaches. We will use computer based modeling techniques to enable us to predict how plague remains silent for long periods before re-emerging as a new disease outbreak. The model inputs will be obtained by measuring rodent burrow temperatures, humidity and local climate conditions in Madagascar, in conjunction with climate, land cover and soil-type datasets. The models will also use data from Y. pestis soil survival experiments which we will obtain under controlled laboratory conditions. We will also use genetic sequencing techniques to investigate the bacterial soil populations that co-habit with Y. pestis as well as uncovering the genes in Y. pestis that are responsible for soil survival.Our data will aid the implementation of surveillance strategies, and identification of the environmental signposts that can predict plague outbreaks, both in Madagascar, and by inference in other plague endemic parts of the world, as well as providing information about plague persistence, spread and therefore potential control measures either before or following a resurgent outbreak.

鼠疫耶尔森氏菌（鼠疫杆菌）是导致鼠疫的细菌，可能是人类已知的最具破坏性的传染病，可能比历史上任何其他微生物（例如黑死病期间）造成的人类死亡人数都多。它的“成功”归功于它具有极强的传染性，如果不加以治疗，通常会在1-2天内死于腺鼠疫、肺鼠疫或败血性鼠疫。啮齿动物、跳蚤和人与人之间的肺炎传播通常被认为是其快速传播的根本原因，尽管很优雅，但有几个事实与这个过于简化的模型不一致。例如，很明显，鼠疫可能从流行地区消失，但在最初的疫情停止几个月或往往几十年后，又卷土重来。在这些宿主和病媒种群消失期间，鼠疫在哪里存在，以及导致鼠疫重新出现的原因，尚未得到详细研究。一些鼠疫杆菌菌株现已获得多种抗生素耐药性，这些菌株传播的激增将对人类健康构成严重风险，因此我们需要了解可能导致重大重新出现事件发生的条件。鼠疫菌是从一种几乎相同的、自由生活的土壤传播的祖先假结核耶尔森氏菌进化而来的，因此土壤被认为是鼠疫菌的储存库，但它如何在这种环境中生存，然后从这种环境中传播还没有得到充分的调查。在其生命周期的这一土壤阶段，鼠疫杆菌可以通过嵌入自生保护性“黏液”层（生物膜）而得到保护，使细菌细胞能够与土壤中的其他细菌、变形虫或线虫形成受保护的联系。在这项研究中，我们将重点放在土壤作为重要的环境水库，在土壤中鼠疫杆菌采取“坐等”的生存方式，当条件有利时，它可以重新进入啮齿动物/人类群体。我们的目标是确定支持鼠疫在土壤中生存和从土壤中重新出现的环境和生物触发因素。为此，我们需要广泛地了解土壤环境，包括小气候、土壤类型和土地覆盖等因素，并测试线虫和变形虫对鼠疫存活的影响。我们的工作将填补我们对鼠疫生态学认识的重大和潜在危险的空白，特别是考虑到世界卫生组织最近将鼠疫杆菌列为重新出现的人畜共患病原体，这一点尤为重要。由于马达加斯加的鼠疫暴发历史记录良好，我们将以马达加斯加为案例研究，利用广泛的科学方法解决这一知识差距。我们将使用基于计算机的建模技术，使我们能够预测鼠疫在作为一种新的疾病爆发重新出现之前是如何长时间保持沉默的。模型输入将结合气候、土地覆盖和土壤类型数据集，通过测量马达加斯加啮齿动物洞穴的温度、湿度和当地气候条件来获得。这些模型还将使用鼠疫杆菌土壤存活实验的数据，我们将在受控的实验室条件下获得这些数据。我们还将使用基因测序技术来研究与鼠疫杆菌共生的细菌土壤种群，以及揭示鼠疫杆菌中负责土壤生存的基因。我们的数据将有助于实施监测战略，确定可在马达加斯加以及通过推断在世界其他鼠疫流行地区预测鼠疫暴发的环境标志，并提供关于鼠疫持续存在、传播以及在疫情再次暴发之前或之后可能采取的控制措施的信息。