Affiliation:
1. Department of Microbiology & Immunology, Columbia University Medical Center, 701 West 168th Street, New York, New York 10032
Abstract
ABSTRACT
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 of
L. pneumophila
to replicate within host cells requires the establishment of a specialized compartment that evades normal phagolysosome fusion called the
Legionella
-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 the
L. pneumophila
arginine repressor homolog, ArgR, is required for maximal intracellular growth in the unicellular host
Acanthamoeba castellanii
. In this study, we present evidence that the concentration of
l
-arginine in the LCV is sensed by ArgR to produce an intracellular transcriptional response. We characterized the
L. pneumophila
ArgR regulon by global gene expression analysis, identified genes highly affected by ArgR, showed that ArgR repression is dependent upon the presence of
l
-arginine, and demonstrated that ArgR-regulated genes are derepressed during intracellular growth. Additional targets of ArgR that may account for the
argR
mutant's intracellular multiplication defect are discussed. These results suggest that
l
-arginine availability functions as a regulatory signal during
Legionella
intracellular growth.
Publisher
American Society for Microbiology
Subject
Molecular Biology,Microbiology
Cited by
34 articles.
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