Inter-kingdom Signaling by the Legionella Quorum Sensing Molecule LAI-1 Modulates Cell Migration through an IQGAP1-Cdc42-ARHGEF9-Dependent Pathway

Sylvia Simon, Ursula Schell, Natalie Heuer, Dominik Hager, Michael F. Albers, Jan Matthias, Felix Fahrnbauer, Dirk Trauner, Ludwig Eichinger, Christian Hedberg, Hubert Hilbi

Research output: Contribution to journalArticle

Abstract

Small molecule signaling promotes the communication between bacteria as well as between bacteria and eukaryotes. The opportunistic pathogenic bacterium Legionella pneumophila employs LAI-1 (3-hydroxypentadecane-4-one) for bacterial cell-cell communication. LAI-1 is produced and detected by the Lqs (Legionella quorum sensing) system, which regulates a variety of processes including natural competence for DNA uptake and pathogen-host cell interactions. In this study, we analyze the role of LAI-1 in inter-kingdom signaling. L. pneumophila lacking the autoinducer synthase LqsA no longer impeded the migration of infected cells, and the defect was complemented by plasmid-borne lqsA. Synthetic LAI-1 dose-dependently inhibited cell migration, without affecting bacterial uptake or cytotoxicity. The forward migration index but not the velocity of LAI-1-treated cells was reduced, and the cell cytoskeleton appeared destabilized. LAI-1-dependent inhibition of cell migration involved the scaffold protein IQGAP1, the small GTPase Cdc42 as well as the Cdc42-specific guanine nucleotide exchange factor ARHGEF9, but not other modulators of Cdc42, or RhoA, Rac1 or Ran GTPase. Upon treatment with LAI-1, Cdc42 was inactivated and IQGAP1 redistributed to the cell cortex regardless of whether Cdc42 was present or not. Furthermore, LAI-1 reversed the inhibition of cell migration by L. pneumophila, suggesting that the compound and the bacteria antagonistically target host signaling pathway(s). Collectively, the results indicate that the L. pneumophila quorum sensing compound LAI-1 modulates migration of eukaryotic cells through a signaling pathway involving IQGAP1, Cdc42 and ARHGEF9.

Original languageEnglish (US)
Article numbere1005307
JournalPLoS Pathogens
Volume11
Issue number12
DOIs
StatePublished - 2015

Fingerprint

Quorum Sensing
Legionella pneumophila
Legionella
Cell Movement
Cell Migration Inhibition
Bacteria
Cell Communication
Host-Pathogen Interactions
Guanine Nucleotide Exchange Factors
Monomeric GTP-Binding Proteins
GTP Phosphohydrolases
Eukaryotic Cells
Eukaryota
Cytoskeleton
Mental Competency
Plasmids
Communication
DNA

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

Cite this

Inter-kingdom Signaling by the Legionella Quorum Sensing Molecule LAI-1 Modulates Cell Migration through an IQGAP1-Cdc42-ARHGEF9-Dependent Pathway. / Simon, Sylvia; Schell, Ursula; Heuer, Natalie; Hager, Dominik; Albers, Michael F.; Matthias, Jan; Fahrnbauer, Felix; Trauner, Dirk; Eichinger, Ludwig; Hedberg, Christian; Hilbi, Hubert.

In: PLoS Pathogens, Vol. 11, No. 12, e1005307, 2015.

Research output: Contribution to journalArticle

Simon, S, Schell, U, Heuer, N, Hager, D, Albers, MF, Matthias, J, Fahrnbauer, F, Trauner, D, Eichinger, L, Hedberg, C & Hilbi, H 2015, 'Inter-kingdom Signaling by the Legionella Quorum Sensing Molecule LAI-1 Modulates Cell Migration through an IQGAP1-Cdc42-ARHGEF9-Dependent Pathway', PLoS Pathogens, vol. 11, no. 12, e1005307. https://doi.org/10.1371/journal.ppat.1005307
Simon, Sylvia ; Schell, Ursula ; Heuer, Natalie ; Hager, Dominik ; Albers, Michael F. ; Matthias, Jan ; Fahrnbauer, Felix ; Trauner, Dirk ; Eichinger, Ludwig ; Hedberg, Christian ; Hilbi, Hubert. / Inter-kingdom Signaling by the Legionella Quorum Sensing Molecule LAI-1 Modulates Cell Migration through an IQGAP1-Cdc42-ARHGEF9-Dependent Pathway. In: PLoS Pathogens. 2015 ; Vol. 11, No. 12.
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