The goal of this project is to better understand the evolution of host adaptation, and to identify genetic innovations that allow free-living bacteria to adapt to eukaryotic hosts. The chosen model is the bacterial order Legionellales, which includes two human pathogens, Legionella and Coxiella.
The main issues addressed here are (i) whether the current ecological diversity of Legionellales is the result of a single event of host-adaptation and (ii) what genetic systems crucial to host-adaptation were invented, that allowed the ecological success of Legionellales.
Two levels of evolutionary scale will be investigated, using next-generation sequencing. First, horizontal transfers and gene gain and loss will be identified by sequencing new genera of Legionellales. Large existing or new metagenomes will be screened for the presence of unknown Legionellales members. The sequence of the last common ancestor of Legionellales will be reconstructed. Second, 200 epidemic and environmental isolates of Legionella will be sequenced and screened for adaptive mutations, to identify new pathogenicity genes.
An automated pipeline will be developed, which will allow going from DNA isolation to a list of potential pathogenicity genes in 3 days.
The results of this hypothesis-driven genomics study will shed new light on the evolution of host adaptation in general and on the evolution and pathogenicity of Legionella and possibly Coxiella. From a translational research point of view, the software developed here will be directly useful in diagnostic and epidemiological applications.