Comparison of related clinical and environmental samples of Legionella pneumophila taken from humans. Rapid adaptations to the human host in Legionella pneumophila

Legionella pneumophila are host-adapted bacteria that infect, and reproduce primarily in aquatic protozoa. Using similar infection mechanisms, they infect human macrophages, and cause Legionnaire's disease and milder Pontiac fever in humans. We hypothesize that, despite these similarities, the hosts are different enough so that there exist a few mutations with high selective value, which would dramatically increase the fitness of Legionella inside the human host. By comparing a large enough number of independent infections, we expect highly adaptive mutations to appear several times, despite the short duration of the typical incubation period (2-10 days). Our analysis found nine genes mutated independently multiple times, including genes potentially involved in virulence and motility, and several premature stop codons in an (outer) membrane protein. As human-to-human transmission is uncommon, fixation of these mutations into the population and spread into the environment is unlikely. Therefore, convergent evolution – here mutations in the same genes observed in independent human infections – could point to adaptations to the accidental human host. These results suggest Legionella pneumophila that despite its ability to infect, replicate, and disperse from amoeabae Legionella may not be fully adapted to human macrophages.