4.1 Virulence and host adaptation assessment of C. burnetii isolates in host-specific and model systems.
In vitro epithelial and macrophage cellular assays that can distinguish C. burnetii strains from different genotypes, host species, and virulence profiles have been established. More recently human and livestock whole-blood assays have been used to identify host-specific differences in the response to pathogens. These systems will be deployed to screen prototype C. burnetii isolates representing clusters of recent isolates from across Europe (derived from WP1/2, with input from phylogenetic analysis in WP3) for replication efficiency and cytokine induction in cattle, sheep, goats, and human cells. Results will be cross validated in a Galleria mellonella model. The aim is to develop a high through-put in vitro phenotyping platform applicable to prospectively grading C. burnetti isolates as to their pathogenic potential and provide in vitro phenotypes for genome association studies in WP4.2.
4.2 Linking C. burnetii genotypes to host species from their distribution in the field
Phylogenetic analysis (WP3) will constitute a starting point to study the adaptation of C. burnetii genotypes to their hosts. Different features associated with genome sequences will be mapped on the phylogeny: (i) metadata from WP1, e.g. host species, nature of the sampled material, clinical outcome; and (ii) experimental in vitro measures of representative isolates from WP4.1. The homogeneity of the distribution of each feature along the phylogeny will be tested to identify lineages characterized by different host ranges in the field or measured phenotypes. The evolution of each feature will be further characterized using appropriate models to study their pace and pattern of evolution, e.g. discrete state transition models to assess transmission patterns among host species. Correlation among the phylogenetic distributions of features will be investigated to assess whether they can be analysed as independent adaptation traits. Based on this overview of phenotypic evolution, we will look for the genetic basis of adaptation of C. burnetii isolates to their host using classical whole genome association studies and alternative, artificial intelligence based, approaches.
WP4 Leads
Prof. Christian Menge
Christian is head of the Friedrich-Loeffler Institute (FLI), Jena, Germany and Administrative Local Representative of the President of FLI. His work focuses on phenotypic characterisation of zoonotic bacteria and development of vaccines and interventions.
Dr. Xavier Bailly
Xavier is a molecular epidemiologist of animal and zoonotic pathogens at INRAE, France. His work uses high-throughput DNA sequencing to understand and characterise livestock pathogens.
