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

点击翻译按钮获取中文摘要

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.