Universität zu Köln

Simon, Sylvia, Schell, Ursula, Heuer, Natalie, Hager, Dominik, Albers, Michael F., Matthias, Jan, Fahrnbauer, Felix, Trauner, Dirk, Eichinger, Ludwig ORCID: 0000-0003-1594-6117, Hedberg, Christian and Hilbi, Hubert ORCID: 0000-0002-5462-9301 (2015). Inter-kingdom Signaling by the Legionella Quorum Sensing Molecule LAI-1 Modulates Cell Migration through an IQGAP1-Cdc42-ARHGEF9-Dependent Pathway. PLoS Pathog., 11 (12). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1553-7374

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Simon, Sylvia UNSPECIFIED UNSPECIFIED UNSPECIFIED Schell, Ursula UNSPECIFIED UNSPECIFIED UNSPECIFIED Heuer, Natalie UNSPECIFIED UNSPECIFIED UNSPECIFIED Hager, Dominik UNSPECIFIED UNSPECIFIED UNSPECIFIED Albers, Michael F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Matthias, Jan UNSPECIFIED UNSPECIFIED UNSPECIFIED Fahrnbauer, Felix UNSPECIFIED UNSPECIFIED UNSPECIFIED Trauner, Dirk UNSPECIFIED UNSPECIFIED UNSPECIFIED Eichinger, Ludwig UNSPECIFIED orcid.org/0000-0003-1594-6117 UNSPECIFIED Hedberg, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Hilbi, Hubert UNSPECIFIED orcid.org/0000-0002-5462-9301 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-384779
DOI:	10.1371/journal.ppat.1005307
Journal or Publication Title:	PLoS Pathog.
Volume:	11
Number:	12
Date:	2015
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1553-7374
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PATHOGEN-HOST INTERACTIONS; AUTOINDUCER SYNTHASE LQSA; RESPONSE REGULATOR LQSR; DICTYOSTELIUM-DISCOIDEUM; PNEUMOPHILA; IQGAP1; GROWTH; VIBRIO; INFECTION; EFFECTOR Multiple languages Microbiology; Parasitology; Virology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/38477