Rapid adaptations of Legionella pneumophila to the human host

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 the similarities in infection mechanisms, the hosts are different enough 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 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 L. pneumophila to infect, replicate in and exit from macrophages, its human-specific adaptations are unlikely to be fixed in the population.

Recurrence, Microevolution, and Spatiotemporal Dynamics of Legionella pneumophila Sequence Type 1905, Portugal, 2014–2022

“…Overall, the observed microevolution across the 12 isolates was marked by 10 SNPs (9 nonsynonymous and 1 synonymous mutations), 4 insertion/deletions, and 1 small recombination event ( Figure 2 ). The low number of SNPs during the 8-year period supports the notion that L. pneumophila evolves at a very slow rate, resulting in substantial temporal and spatial conservation, as previously reported ( 9 , 10 ). When compared with PtVFX/2014, all isolates presented a recombination event in an ≈2.5-kb region (contig 8, PtVFX/2014_08985-08995) belonging to the type IVA secretion system, which is associated with the survival of the bacteria in the environment ( 11 ).…”

“…Although we cannot make conclusions about a potential adaptive role of the observed mutations, it has been hypothesized that mutations found exclusively in clinical isolates, as in our study, might reflect human-specific adaptation ( 10 ). L. pneumophila can infect and replicate in human alveolar macrophages, but human-to-human transmission is assumed to be rare; thus, fixation of those mutations into L. pneumophila circulating in the human population is unlikely ( 10 , 12 ). Still, it has been proposed that the recent expansion of L. pneumophila in manmade water systems, together with the widespread distribution of specific clones at global scale, aligns with the potential dissemination between humans or from humans to the environment ( 13 ).…”

“…fraseri and is located within a larger genomic region that contains known Dot/Icm substrates (3). Although we cannot make conclusions about a potential adaptive role of the observed mutations, it has been hypothesized that mutations found exclusively in clinical isolates, as in our study, might reflect human-specific adaptation (10). L. pneumophila can infect and replicate in human alveolar macrophages, but human-to-human transmission is assumed to be rare; thus, fixation of those mutations into L. pneumophila circulating in the human population is unlikely (10,12).…”

Severe Legionnaires’ disease

“…LD is an evolutionary dead-end for Legionella ; it is either cleared by the immune system or results in the death of the patient. No or very rare commensal status has been reported for Legionella and there is no human-to-human transmission, suggesting that any human-specific adaptations that may occur during infection are unlikely to be fixed in the population [ 47 ]; this may partly explain the low level of antibiotic resistance.…”