PRedicting the ecological niche of human pathogens Infectious strains as a key determinant of infectious disease eMErgence – PRIME

The great majority of emerging infectious diseases (EIDs) are dominated by zoonoses (62 to 75%), with most of these being caused by pathogens with a wildlife origin. Among the 250 EIDs that affect humans, most are associated with areas of tropical rainforest, which provide EID ‘hotspots’, especially in freshwater ecosystems. Their emergence is closely linked to rapid socio-economic and land-use/environmental changes leading to rapid changes in wildlife diversity. Global changes such as climate change are also suspected to underpin changes in infectious disease systems (microbe/host reservoir or vector/environment) and/or host prevalence. Whatever the source of these changes, they impact pathogen transmission and modify the exposure of the host to potential environmental pathogens. However, considering environmental pathways of generalist pathogens without considering the role of wildlife in providing zoonotic pools from which pathogens can emerge/re-emerge is limiting our understanding of disease outbreak. Whilst most studies have focused on determining the genetic diversity of human pathogens isolated from clinical samples (i.e. infectious strains of pathogens), information about the diversity of environmental strains (i.e. both infectious and non-infectious) of these pathogens and the distribution and availability of infectious strains in the environment is considerably lacking. Using Mycobacterium ulcerans (MU), the causative agent of Buruli ulcer disease (BU), we aim to characterize the distribution of infectious and non-infectious MU strains across tropical freshwater host communities in space and time. Specific focus would be on comparing the ecological niche of the various clinical strains with regard to those only found in the environment, thus underpinning the true pathways of infection, notably in terms of local host community composition and foodweb structure. This ecological approach to EIDs is necessary to determine which biotic and environmental factors underpin the selection and transmission of these infectious strains to humans. Here, we propose a new approach to the study of EIDs by analysing pathogen dynamics in the environment via a community-based approach that relies on the multidisciplinarity of PRIME, which combines aquatic ecology, microbiology, epidemiology of infectious diseases, genetics and mathematical modelling. New methodological tools will be developed such as culture systems for environmental pathogens, Single-Nucleotide Polymorphisms (SNPs) and environmental DNA (eDNA) approaches based on Whole-Genome-Sequencing (WGS) to study strain diversity in situ. Based on preliminary results, we expect to find a wide diversity of strains in the environment but that only a minority of these strains could be pathogenic for humans (found in clinical samples). We also suspect the pathogenic (infectious) strains to be found in separate ecological niches to the non-pathogenic ones, for instance associated to key host species that could promote contact with and transmission to humans. Finally, we expect the spatio-temporal dynamics of the various strains to follow the dynamics of their host and the infectious risk to fluctuate over the year depending on specific biotic and abiotic factors.