title: Dual function of tropodithietic acid as antibiotic and signaling molecule in global gene regulation of the probiotic bacterium Phaeobacter inhibens.
abstract: Antibiotics are typically regarded as microbial weapons, but whereas their function at concentrations lethal for bacteria is often well characterized, the role of antibiotics at much lower concentrations as possibly found under natural conditions remains poorly understood. By using whole-transcriptome analyses and phenotypic screenings of the marine bacterium Phaeobacter inhibens we found that the broad-spectrum antibiotic tropodithietic acid (TDA) causes the same regulatory effects in quorum sensing (QS) as the common signaling molecule N-acyl-homoserine lactone (AHL) at concentrations 100-fold lower than the minimal inhibitory concentration against bacteria. Our results show that TDA has a significant impact on the expression of ~10% of the total genes of P. inhibens, in the same manner as the AHL. Furthermore, TDA needs the AHL associated LuxR-type transcriptional regulator, just as the AHL molecule. Low concentrations of antibiotics can obviously have a strong influence on the global gene expression of the bacterium that produces it and drastically change the metabolism and behaviour of the bacterium. For P. inhibens this includes motility, biofilm formation and antibiotic production, all important for settlement on new host-associated surfaces. Our results demonstrate that bacteria can produce antibiotics not only to antagonise other bacteria, but also to mediate QS like endogenous AHL molecules.
authors.affiliation: Institute for Chemistry and Biology of the Marine Environment (ICBM), University of Oldenburg, 26129, Oldenburg, Germany.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Beyersmann
authors.affiliation: Helmholtz Centre for Infection Research, 38124, Braunschweig, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Tomasch
authors.affiliation: Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
authors.forename: Kwangmin
authors.initials: K
authors.lastname: Son
authors.affiliation: Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.|Institute for Environmental Engineering, Department of Civil, Environmental and Geomatic Engineering, Eidgenössische Technische Hochschule (ETH) Zürich, Zurich, 8093, Switzerland.
authors.forename: Roman
authors.initials: R
authors.lastname: Stocker
authors.affiliation: Leibniz-Institute DSMZ - German Collection of Microorganisms and Cell Cultures GmbH, 38124, Braunschweig, Germany.
authors.forename: Markus
authors.identifier: http://orcid.org/0000-0002-5144-6200
authors.initials: M
authors.lastname: Göker
authors.affiliation: Helmholtz Centre for Infection Research, 38124, Braunschweig, Germany.
authors.forename: Irene
authors.initials: I
authors.lastname: Wagner-Döbler
authors.affiliation: Institute for Chemistry and Biology of the Marine Environment (ICBM), University of Oldenburg, 26129, Oldenburg, Germany.
authors.forename: Meinhard
authors.initials: M
authors.lastname: Simon
authors.affiliation: Institute for Chemistry and Biology of the Marine Environment (ICBM), University of Oldenburg, 26129, Oldenburg, Germany. t.brinkhoff@icbm.de.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Brinkhoff
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D019295:Computational Biology / Q000379:methods; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D008954:Models, Biological; D009154:Mutation; D019936:Probiotics; D053038:Quorum Sensing / Q000187:drug effects; D016992:Rhodobacter / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*; D059467:Transcriptome; D014334:Tropolone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; C527336:tropodithietic acid; D014334:Tropolone