Decomposing virulence: host, pathogen, and microbiota contributions

点击翻译按钮获取中文摘要

Virulence describes the negative health or fitness effect of an pathogen, and there is long-standing interest in understanding how virulence changes over evolutionary time. Virulence will be determined by pathogen and host factors, but it is not trivial to understand the degree to which each partner affects virulence patterns. Nonetheless, we can start to understand the drivers of virulence changes by “decomposing” virulence into pathogen and host components: The pathogen contributes towards virulence through a) exploitation, that is its ability to replicate inside the host and b) per parasite pathogenicity, that is the amount of damage that it does per pathogen. The host affects virulence through c) resistance, that is suppression of pathogen growth and d) tolerance, that is limiting the negative health effects of a given infection load. More recently there has been a blossoming of interest in the tripartite interaction between host, pathogen and microbiota, and the role that microbiota play in pathogen virulence evolution. In this grant we propose to fully decompose virulence into all four host and pathogen components (a-d), whilst taking the interaction with microbiota into account. We will use pathogens experimentally evolved in the presence and absence of a species of cuticular microbiota resulting from funding period one of the Research Unit FOR 5026. We will first test the virulence of the ancestral and two evolved bacterial pathogens in the context of 1) the experimental presence and absence of microbiota, 2A) host sex, and 3) different host populations. In each case we will then estimate the contribution of the host and pathogen components (a-d) to these virulence patterns. To uncover potential host drivers of the virulence patterns in 2A, in 2B we will analyse the transcriptional responses of females and males upon systemic infection with the ancestral and evolved pathogens. The transcriptional objective is expected to compliment inferences from the virulence decomposition analysis, and vice versa. Overall, this approach means that we can simultaneously assess effects from the host and pathogen perspective on two levels: first broad-scale virulence patterns and subsequently a deeper understanding of evolutionary changes through a virulence decomposition. This project will give insight into the generalisability of virulence patterns, it will help us to uncover hidden drivers of virulence, and it will give insight into the generalisability of the components of virulence.