1887

Abstract

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 the similarities in infection mechanisms, the hosts are different enough that there exist high-selective value mutations that would dramatically increase the fitness of 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 other is a gene coding for an EAL-domain-containing protein involved in cyclic-di-GMP regulation, which in turn modulates flagellar activity. The clinical strain, carrying the mutated EAL-domain-containing homologue, grows faster in macrophages than the wild-type strain, and thus appears to be better adapted to the human host. As human-to-human transmission is very rare, fixation of these mutations into the population and spread into the environment is unlikely. Therefore, parallel 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 the ability of to infect, replicate in and exit from macrophages, its human-specific adaptations are unlikely to be fixed in the population.

Funding
This study was supported by the:
  • Science for Life Laboratory (Award Swedish Genomes and Biodiversity 2015)
    • Principle Award Recipient: LionelGuy
  • Carl Tryggers Stiftelse för Vetenskaplig Forskning (Award CTS 15:184)
    • Principle Award Recipient: LionelGuy
  • Vetenskapsrådet (Award 2017-03709)
    • Principle Award Recipient: LionelGuy
  • Fonds de recherche du Québec – Nature et technologies (Award FRQNT B3X)
    • Principle Award Recipient: KiranParanjape
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2023-03-22
2024-04-24
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