RpoS co-operates with other factors to induce Legionella pneumophila virulence in the stationary phase

Mol Microbiol. 2001 Jun;40(5):1201-14. doi: 10.1046/j.1365-2958.2001.02465.x.


Legionella pneumophila replicates within amoebae and macrophages and causes the severe pneumonia Legionnaires' disease. When broth cultures enter the post-exponential growth (PE) phase or experience amino acid limitation, L. pneumophila accumulates the stringent response signal (p)ppGpp and expresses traits likely to promote transmission to a new phagocyte. The hypothesis that a stringent response mechanism regulates L. pneumophila virulence was bolstered by our finding that the avirulent mutant Lp120 contains an internal deletion in the gene encoding the stationary phase sigma factor RpoS. To test directly whether RpoS co-ordinates virulence with stationary phase, isogenic wild-type, rpoS-120 and rpoS null mutant strains were constructed and analysed. PE phase L. pneumophila became cytotoxic by an RpoS-independent pathway, but their sodium sensitivity and maximal expression of flagellin required RpoS. Likewise, full induction of sodium sensitivity by experimentally induced (p)ppGpp synthesis required RpoS. To replicate efficiently in macrophages, L. pneumophila used both RpoS-dependent and -independent pathways. Like those containing the dotA type IV secretory apparatus mutant, phagosomes harbouring either rpoS or dotA rpoS mutants rapidly acquired the late endosomal protein LAMP-1, but not the lysosomal marker Texas red-ovalbumin. Together, the data support a model in which RpoS co-operates with other regulators to induce L. pneumophila virulence in the PE phase.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bacterial Proteins / drug effects
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Cell Compartmentation
  • Cell Division
  • Cloning, Molecular
  • Endosomes / metabolism
  • Flagellin / genetics
  • Flagellin / metabolism
  • Guanosine Tetraphosphate / metabolism
  • Legionella pneumophila / genetics
  • Legionella pneumophila / growth & development
  • Legionella pneumophila / pathogenicity*
  • Macrophages / microbiology
  • Mice
  • Mice, Inbred Strains
  • Mutation
  • Sigma Factor / drug effects
  • Sigma Factor / genetics
  • Sigma Factor / metabolism*
  • Sodium / pharmacology
  • Stress, Physiological
  • Virulence / genetics


  • Bacterial Proteins
  • Sigma Factor
  • sigma factor KatF protein, Bacteria
  • Flagellin
  • Guanosine Tetraphosphate
  • Sodium