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

PLoS Pathogens

Hubert Hilbi¹  Jan Matthias¹  Dirk Trauner²  Ludwig Eichinger²  Michael F. Albers²  Dominik Hager³  Felix Fahrnbauer³  Christian Hedberg³  Ursula Schell⁴  Sylvia Simon⁵  Natalie Heuer⁵ 

[1] Department of Chemistry and Umeå Center for Microbial Research, Umeå University, Umeå, Sweden;Department of Chemistry, Ludwig-Maximilians University, Munich, Germany;Institute of Biochemistry I, University of Cologne, Cologne, Germany;Institute of Medical Microbiology, University of Zürich, Zürich, Switzerland;Max von Pettenkofer Institute, Ludwig-Maximilians University, Munich, Germany

关键词: Legionella pneumophila;    Cell migration;    Dictyostelium discoideum;    Macrophages;    Host cell migration;    Guanosine triphosphatase;    Amoebas;    Small interfering RNAs;   

DOI  :  10.1371/journal.ppat.1005307

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY