ArticlePLoS pathogens2012
Experimental evolution of Legionella pneumophila in mouse macrophages leads to strains with altered determinants of environmental survival.
Article in PLoS pathogens, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 79 citations in OpenAlex.
- Simulating the host niche: balancing complexity and control in the experimental evolution of antibiotic resistance and pathoadaptation.Microbiology (Reading, England) · 2026Review
- Longitudinal Antimicrobial Susceptibility Shifts in EnvironmentalPathogens (Basel, Switzerland) · 2026Article
- Immune-adaptive pathogen variation reveals targetable mediators of gram-positive bacterial killing in macrophages.Science advances · 2026Article
- A bacterial toxin-antitoxin system involved in an unusual response to genotoxic stress.EMBO reports · 2025Article
- Host-Specific Adaptation of Legionella pneumophila to Single and Multiple Hosts.Molecular biology and evolution · 2025Article
- Foresight 2035: a perspective on the next decade of research on the management of Legionella spp. in engineered aquatic environments.FEMS microbiology reviews · 2025Review
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- A random mutagenesis screen enriched for missense mutations in bacterial effector proteins.G3 (Bethesda, Md.) · 2024Article
- Development of heat-shock resistance inApplied and environmental microbiology · 2023Article
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- Intracellular Experimental Evolution ofACS infectious diseases · 2023Article
- Adaptation to an amoeba host drives selection of virulence-associated traits in Vibrio cholerae.The ISME journal · 2022Article
- SdhA blocks disruption of the Legionella-containing vacuole by hijacking the OCRL phosphatase.Cell reports · 2021Article
- Article
- Non-pathogenic Escherichia coli acquires virulence by mutating a growth-essential LPS transporter.PLoS pathogens · 2020Article
- Combinatorial selection in amoebal hosts drives the evolution of the human pathogen Legionella pneumophila.Nature microbiology · 2020Article
- Components of the endocytic and recycling trafficking pathways interfere with the integrity of the Legionella-containing vacuole.Cellular microbiology · 2020Article
- Immunometabolism at the interface between macrophages and pathogens.Nature reviews. Immunology · 2019Review
- AttenuatedBioMed research international · 2019Article
- Identification and characterization of a large family of superbinding bacterial SH2 domains.Nature communications · 2018Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
The Gram-negative bacterium, Legionella pneumophila, is a protozoan parasite and accidental intracellular pathogen of humans. We propose a model in which cycling through multiple protozoan hosts in the environment holds L. pneumophila in a state of evolutionary stasis as a broad host-range pathogen. Using an experimental evolution approach, we tested this hypothesis by restricting L. pneumophila to growth within mouse macrophages for hundreds of generations. Whole-genome resequencing and high-throughput genotyping identified several parallel adaptive mutations and population dynamics that led to improved replication within macrophages. Based on these results, we provide a detailed view of the population dynamics of an experimentally evolving bacterial population, punctuated by frequent instances of transient clonal interference and selective sweeps. Non-synonymous point mutations in the flagellar regulator, fleN, resulted in increased uptake and broadly increased replication in both macrophages and amoebae. Mutations in multiple steps of the lysine biosynthesis pathway were also independently isolated, resulting in lysine auxotrophy and reduced replication in amoebae. These results demonstrate that under laboratory conditions, host restriction is sufficient to rapidly modify L. pneumophila fitness and host range. We hypothesize that, in the environment, host cycling prevents L. pneumophila host-specialization by maintaining pathways that are deleterious for growth in macrophages and other hosts.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.