ArgR-Regulated Genes Are Derepressed in the Legionella -Containing Vacuole

Legionella pneumophila is an intracellular pathogen that infects protozoa in aquatic environments and when inhaled by susceptible human hosts replicates in alveolar macrophages and can result in the often fatal pneumonia called Legionnaires' disease. The ability ofL. pneumophila to replicate within host cells requires the establishment of a specialized compartment that evades normal phagolysosome fusion called theLegionella -containing vacuole (LCV). Elucidation of the biochemical composition of the LCV and the identification of the regulatory signals sensed during intracellular replication are inherently challenging.l -Arginine is a critical nutrient in the metabolism of both prokaryotic and eukaryotic organisms. We showed that theL. pneumophila arginine repressor homolog, ArgR, is required for maximal intracellular growth in the unicellular hostAcanthamoeba castellanii . In this study, we present evidence that the concentration ofl -arginine in the LCV is sensed by ArgR to produce an intracellular transcriptional response. We characterized theL. pneumophila ArgR regulon by global gene expression analysis, identified genes highly affected by ArgR, showed that ArgR repression is dependent upon the presence ofl -arginine, and demonstrated that ArgR-regulated genes are derepressed during intracellular growth. Additional targets of ArgR that may account for theargR mutant's intracellular multiplication defect are discussed. These results suggest thatl -arginine availability functions as a regulatory signal duringLegionella intracellular growth.