Co-ordination of legionella pneumophila virulence with entry into stationary phase by ppGpp.
Legionella pneumophila survives in aquatic environments, but replicates within amoebae or the alveolar macrophages of immunocompromised individuals. Here, the signal transduction pathway that co-ordinates L. pneumophila virulence expression in response to amino acid depletion was investigated. To facilitate kinetic and genetic studies, a phenotypic reporter of virulence was engineered by fusing flaA promoter sequences to a gene encoding green fluorescent protein. When subjected to amino acid depletion, L. pneumophila accumulated ppGpp and converted from a replicative to a virulent state, as judged by motility and sodium sensitivity. ppGpp appeared to initiate this response, as L. pneumophila induced to express the Escherichia coli RelA ppGpp synthetase independently of nutrient depletion accumulated ppGpp, exited the exponential growth phase and expressed flaAgfp, motility, sodium sensitivity, cytotoxicity and infectivity, five traits correlated with virulence. Although coincident with the stationary phase, L. pneumophila virulence expression appeared to require an additional factor: mutant Lp120 accumulated ppGpp and acquired two stationary phase traits but none of six virulence phenotypes analysed. We propose that, when nutrients are limiting, ppGpp acts as an alarmone, triggering the expression of multiple traits that enable L. pneumophila to escape its spent host, to survive and disperse in the environment and to re-establish a protected intracellular replication niche.
Hammer
B K
BK
Department of Microbiology and Immunology, The University of Michigan Medical School, 6734 Medical Sciences Building II, Ann Arbor, MI 48109-0620, USA.
Swanson
M S
MS
D000596:Amino Acids / Q000378:metabolism; D002455:Cell Division; D005408:Flagellin / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D049452:Green Fluorescent Proteins; D006159:Guanosine Tetraphosphate / Q000378:metabolism*; D007700:Kinetics; D016952:Legionella pneumophila / Q000235:genetics / Q000472:pathogenicity*; D008025:Ligases / Q000235:genetics; D008164:Luminescent Proteins; D009154:Mutation; D010641:Phenotype; D011401:Promoter Regions, Genetic; D015398:Signal Transduction / Q000235:genetics; D014774:Virulence / Q000235:genetics
D000596:Amino Acids; D008164:Luminescent Proteins; D005408:Flagellin; C067138:flaA protein, bacteria; D049452:Green Fluorescent Proteins; D006159:Guanosine Tetraphosphate; D008025:Ligases; C028812:guanosine 3',5'-polyphosphate synthetases