The Legionella pneumophila Life Cycle: Connections between Growth Phase, Virulence Expression, and Replication Vacuole Biogenesis

To persist in the environment, Legionella pneumophila that is confronted with feeding amoebae, must avoid digestion and instead establish a protected site for intracellular replication. After exhausting the resources of its host, the bacterial progeny must vacate the premises to search out a more fertile locale. When L. pneumophila encounters grazing amoebae, its prowess as a parasite becomes paramount. A model for the L. pneumophila life cycle in which growth phase determines virulence expression and replication vacuole biogenesis has been provided in this chapter. A striking observation made by Brenda Byrne motivated the authors' investigation of L. pneumophila virulence regulation. When broth cultures of L. pneumophila exit the exponential growth (E) phase, the bacteria become osmotically resistant, sodium sensitive, cytotoxic, motile, infectious, and competent to evade macrophage lysosomes. Results obtained by four independent experimental approaches strengthen the hypothesis that L. pneumophila survives and replicates within lysosomal compartments. First, virtually every vacuole that harbors more than five bacteria also contains LAMP-1. Second, bacteria within endosomal vacuoles are viable, as judged by their capacity to respond to a metabolic inducer by expressing a gfp reporter gene. Third, replicating bacteria obtained from macrophages, but not broth, are acid resistant. Finally, inhibition of vacuole acidification and maturation by bafilomycin A1 or other agents actually inhibits bacterial replication.