A two-component regulator induces the transmission phenotype of stationary-phase Legionella pneumophila

Authors

  • Brian K. Hammer,

    1. Department of Microbiology and Immunology, University of Michigan Medical School, 6734 Medical Sciences Building II, Ann Arbor, MI 48109-0620, USA.
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    • Present address: Department of Molecular Biology, Princeton University, Princeton, NJ 08544-1014, USA.

  • Eiko S. Tateda,

    1. Department of Microbiology and Immunology, University of Michigan Medical School, 6734 Medical Sciences Building II, Ann Arbor, MI 48109-0620, USA.
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  • Michele S. Swanson

    Corresponding author
    1. Department of Microbiology and Immunology, University of Michigan Medical School, 6734 Medical Sciences Building II, Ann Arbor, MI 48109-0620, USA.
    • *For correspondence: E-mail mswan son@umich.edu; Tel. (+1) 734 647 7295; Fax (+1) 734 764 3562.

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  • *For correspondence: E-mail mswan son@umich.edu; Tel. (+1) 734 647 7295; Fax (+1) 734 764 3562.

Summary

Pathogenic Legionella pneumophila evolved as a parasite of aquatic amoebae. To persist in the environment, the microbe must be proficient at both replication and transmission. In laboratory cultures, as nutrients become scarce a stringent response-like pathway coordinates exit from the exponential growth phase with induction of traits correlated with virulence, including motility. A screen for mutants that express the flagellin gene poorly identified five activators of virulence: LetA/LetS, a two-component regulator homologous to GacA/GacS of Pseudomonas and SirA/BarA of Salmonella; the stationary-phase sigma factor RpoS; the flagellar sigma factor FliA; and a new locus, letE. Unlike wild type, post-exponential-phase letA and letS mutants were not motile, cytotoxic, sodium sensitive or proficient at infecting macrophages. L. pneumophila also required fliA to become motile, cytotoxic and to infect macrophages efficiently and letE to express sodium sensitivity and maximal motility and cytotoxicity. When induced to express RelA, all of the strains exited the exponential phase, but only wild type converted to the fully virulent form. In contrast, intracellular replication was independent of letA, letS, letE or fliA. Together, the data indicate that, as the nutrient supply wanes, ppGpp triggers a regulatory cascade mediated by LetA/ LetS, RpoS, FliA and letE that coordinates differentiation of replicating L. pneumophila to a transmissible form.

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