SigmaS controls multiple pathways associated with intracellular multiplication of Legionella pneumophila.
Legionella pneumophila is the causative agent of the severe and potentially fatal pneumonia Legionnaires' disease. L. pneumophila is able to replicate within macrophages and protozoa by establishing a replicative compartment in a process that requires the Icm/Dot type IVB secretion system. The signals and regulatory pathways required for Legionella infection and intracellular replication are poorly understood. Mutation of the rpoS gene, which encodes sigma(S), does not affect growth in rich medium but severely decreases L. pneumophila intracellular multiplication within protozoan hosts. To gain insight into the intracellular multiplication defect of an rpoS mutant, we examined its pattern of gene expression during exponential and postexponential growth. We found that sigma(S) affects distinct groups of genes that contribute to Legionella intracellular multiplication. We demonstrate that rpoS mutants have a functional Icm/Dot system yet are defective for the expression of many genes encoding Icm/Dot-translocated substrates. We also show that sigma(S) affects the transcription of the cpxR and pmrA genes, which encode two-component response regulators that directly affect the transcription of Icm/Dot substrates. Our characterization of the L. pneumophila small RNA csrB homologs, rsmY and rsmZ, introduces a link between sigma(S) and the posttranscriptional regulator CsrA. We analyzed the network of sigma(S)-controlled genes by mutational analysis of transcriptional regulators affected by sigma(S). One of these, encoding the L. pneumophila arginine repressor homolog gene, argR, is required for maximal intracellular growth in amoebae. These data show that sigma(S) is a key regulator of multiple pathways required for L. pneumophila intracellular multiplication.
Hovel-Miner
Galadriel
G
Department of Microbiology, Columbia University Medical Center, 701 West 168th Street, New York, NY 10032, USA.
Pampou
Sergey
S
Faucher
Sebastien P
SP
Clarke
Margaret
M
Morozova
Irina
I
Morozov
Pavel
P
Russo
James J
JJ
Shuman
Howard A
HA
Kalachikov
Sergey
S
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D004023:Dictyostelium / Q000382:microbiology*; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D016952:Legionella pneumophila / Q000254:growth & development / Q000472:pathogenicity / Q000502:physiology*; D012808:Sigma Factor / Q000235:genetics / Q000502:physiology*; D014774:Virulence; D037521:Virulence Factors / Q000096:biosynthesis
D001426:Bacterial Proteins; D012808:Sigma Factor; D037521:Virulence Factors; C069567:sigma factor KatF protein, Bacteria