| Legionella pneumophila has a unique intracellular lifestyle characterized by the formation of a specialized compartment that supports bacterial replication. Legionella species replicate in unicellular protozoa in the environment and alveolar macrophages in susceptible human hosts. Replication within alveolar macrophages can result in the severe and often fatal pneumonia Legionnaires' disease. Intracellular survival and growth require that L. pneumophila manipulate host endocytic trafficking by an unusual process indicative of complex regulation. Genes associated with L. pneumophila intracellular multiplication encode a secretion system, translocated effector proteins, and regulators of gene expression. Here, I investigate L. pneumophila intracellular growth through the analysis of transcriptional regulators. The alternative sigma factor, sigma S is used as a tool to investigate Legionella transcriptional networks and identify regulators required for intracellular multiplication. I determined that sigmaS controls multiple pathways associated with the intracellular growth of Legionella. I also found that the transcription factor ArgR is required for intracellular multiplication and controls transcription in response to L-arginine. Evidence is presented that L-arginine availability affects gene expression during intracellular growth. Thus, this thesis contributes to our understanding of the transcriptional regulation of L. pneumophila intracellular multiplication. |
