Genomic Changes During the Evolution of theCoxiellaGenus Along the Parasitism-Mutualism Continuum

AbstractThe Coxiellaceae family is composed of five genera showing lifestyles ranging from free-living to symbiosis. Among them,Coxiella burnetiiis a well-known pathogen causing Q fever in humans. This bacterium presents both intracellular (parasitic) and environmental (resistant) forms. Recently, several environmentalCoxiellagenomes have been reported, among which several have come from intracellular mutualistic symbionts of ticks, termedCoxiella-like endosymbionts. We sequenced two newCoxiella-LE genomes fromDermacentor marginatus(CLEDm) andOrnithodoros maritimus(CLEOmar) ticks, the latter belonging to theC. burnetiilineage. Using these newly sequencedCoxiella-LEs and 43 Coxiellaceae genomes, we conducted comparative genomic and phylogenomic analyses to increase our knowledge ofC. burnetiipathogenicity and the emergence ofCoxiella-LEs. Results highlight the probably parasitic nature of the common ancestor of the Coxiellaceae. Indeed, the virulence factor Dot/Icm T4 Secretion System is present in most, but not all, Coxiellaceae. Whereas it is part of a putative pathogenic island inC. burnetii, it has been entirely lost or inactivated inCoxiella-LEs, suggesting its importance in pathogenesis. Additionally, we found that a Sha/Mrp antiporter was laterally acquired in theC. burnetiilineage. This antiporter might be involved in alkali resistance and the development of the resistant form that is able to persist in the environment for long periods of time. The Sha operon is eroded or absent inCoxiella-LEs. Finally, we found that allCoxiellarepresentatives produce B vitamins and co-factors indicating a pre-adaptation ofCoxiellato mutualism with hematophagous arthropods. Accordingly, the ancestor ofC. burnetiiandCoxiella-LEs was likely a parasitic bacterium able to manipulate its host cell and to produce vitamins and co-factors for its own use.