Rapid, in-patient adaptations of Legionella pneumophila to the human host

Microbial Genomics(2022)

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Abstract
Legionella pneumophila are host-adapted bacteria that infect and reproduce primarily in amoeboid protists. Using similar infection mechanisms, they infect human macrophages, and cause Legionnaires' disease, an atypical pneumonia, and the milder Pontiac fever. We hypothesized that, despite these similarities, the hosts are different enough so that there exist high-selective value mutations that would dramatically increase the fitness of Legionella inside the human host. By comparing a large number of isolates from independent infections, we identified two genes, mutated in three unrelated patients, despite the short duration of the incubation period (2-14 days). One is a gene coding for an outer membrane protein (OMP) belonging to the OmpP1/FadL family. The clinical strain, carrying the mutated OMP homolog, grows faster in macrophages than the wild type strain, and thus appears to be better adapted to the human host. The other is a gene coding for a protein involved in cyclic-di-GMP regulation, which in turn modulates flagellar activity. As human-to-human transmission is very rare, 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 that despite its ability to infect, replicate, and disperse from amoebae, L. pneumophila is not well adapted to the human host. ### Competing Interest Statement The authors have declared no competing interest.
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