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Communication in bacterial biofilms

English title Communication in bacterial biofilms
Applicant Eberl Leo
Number 169307
Funding scheme Project funding (Div. I-III)
Research institution Institut für Pflanzen- und Mikrobiologie Universität Zürich
Institution of higher education University of Zurich - ZH
Main discipline Experimental Microbiology
Start/End 01.01.2017 - 31.05.2020
Approved amount 756'000.00
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All Disciplines (2)

Discipline
Experimental Microbiology
Molecular Biology

Keywords (5)

Pseudomonas putida; extracellular polysaccharide; Quorum sensing; biofilm matrix; Burkholderia cenocepacia

Lay Summary (German)

Lead
Forschungsergebnisse der letzten Jahre haben eindrucksvoll gezeigt, dass Bakterien in der Natur überwiegend als sessile, oberflächen-assoziierte Lebensgemeinschaften, sogenannten Biofilmen, existieren. Auch im medizinischen Bereich finden Biofilme zunehmend Beachtung, da man mittlerweile weiss, dass viele persistente und chronische bakterielle Infektionen eng mit der Ausbildung von Biofilmen verknüpft sind. Die Tatsache, dass die Biofilm-Bakterien im Vergleich zu planktonischen Zellen eine bis zu 1000-fach höhere Resistenz gegenüber Antibiotika verleiht und sie zudem besser vor der Immunabwehr des Wirtes schützt, macht diese Form bakterieller Infektionen besonders problematisch. Viele Bakterien verfügen über Zell-Zell-Kommunikationssysteme, die häufig nicht nur die Expression von Virulenzfaktoren sondern auch die Ausbildung von Biofilmen steuern. In welcher Weise diese Kommunikationssysteme die Biofilmbildung beeinflussen ist jedoch wenig untersucht.
Lay summary
Im Rahmen des Forschungsprojektes soll die Rolle bakterieller Kommunikation für die Biosynthese von extrazellulärer polymerer Substanzen (EPS), die eine Matrix bilden, in der die Biofilm-Bakterien vollständig eingebettet sind. Diese EPS-Schicht gewährt den Zellen einen vermehrten Schutz gegenüber der Immunantwort des Wirts und ist zum Teil auch für die erhöhte Resistenz gegenüber Antibiotika und Bioziden verantwortlich. Mit Hilfe verschiedener molekularer und mikroskopischer Techniken soll die temporäre und räumliche Biosynthesis von Matrix-Komponenten untersucht werden. Zudem soll aufgeklärt werden, unter welchen Bedingungen bakterielle Kommunikation zwischen benachbarten Zellen erfolgt und wann Zellen Eigengespräche führen, sich also selbst induzieren und damit egoistisches Verhalten regulieren. Ein vertieftes Verständnis dieser grundlegenden Fragen der Biofilmbildung könnte die Entwicklung neuer terapeutischer Ansätze zur Bekämpfung und Vermeidung von Biofilminfektionen massgeblich beschleunigen.
Direct link to Lay Summary Last update: 25.11.2016

Responsible applicant and co-applicants

Employees

Publications

Publication
Copper resistance genes of Burkholderia cenocepacia H111 identified by transposon sequencing
Higgins Steven, Gualdi Stefano, Pinto‐Carbó Marta, Eberl Leo (2020), Copper resistance genes of Burkholderia cenocepacia H111 identified by transposon sequencing, in Environmental Microbiology Reports, 12(2), 241-249.
Genetic architecture constrains exploitation of siderophore cooperation in the bacterium Burkholderia cenocepacia
Sathe Santosh, Mathew Anugraha, Agnoli Kirsty, Eberl Leo, Kümmerli Rolf (2019), Genetic architecture constrains exploitation of siderophore cooperation in the bacterium Burkholderia cenocepacia, in Evolution Letters, 3(6), 610-622.
Key Players and Individualists of Cyclic-di-GMP Signaling in Burkholderia cenocepacia
Richter Anja M., Fazli Mustafa, Schmid Nadine, Shilling Rebecca, Suppiger Angela, Givskov Michael, Eberl Leo, Tolker-Nielsen Tim (2019), Key Players and Individualists of Cyclic-di-GMP Signaling in Burkholderia cenocepacia, in Frontiers in Microbiology, 9, 3286.
Burkholderia cenocepacia utilizes a type VI secretion system for bacterial competition.
Spiewak Helena L, Shastri Sravanthi, Zhang Lili, Schwager Stephan, Eberl Leo, Vergunst Annette C, Thomas Mark S (2019), Burkholderia cenocepacia utilizes a type VI secretion system for bacterial competition., in MicrobiologyOpen, 774-774.
Types and origins of bacterial membrane vesicles
Toyofuku Masanori, Nomura Nobuhiko, Eberl Leo (2019), Types and origins of bacterial membrane vesicles, in Nature Reviews Microbiology, 17(1), 13-24.
Biosynthesis of fragin is controlled by a novel quorum sensing signal
Jenul Christian, Sieber Simon, Daeppen Christophe, Mathew Anugraha, Lardi Martina, Pessi Gabriella, Hoepfner Dominic, Neuburger Markus, Linden Anthony, Gademann Karl, Eberl Leo (2018), Biosynthesis of fragin is controlled by a novel quorum sensing signal, in Nature Communications, 9(1), 1297-1297.
The afc antifungal activity cluster, which is under tight regulatory control of ShvR, is essential for transition from intracellular persistence of Burkholderia cenocepacia to acute pro-inflammatory infection
Gomes Margarida C., Tasrini Yara, Subramoni Sujatha, Agnoli Kirsty, Feliciano Joana R., Eberl Leo, Sokol Pamela, O’Callaghan David, Vergunst Annette C. (2018), The afc antifungal activity cluster, which is under tight regulatory control of ShvR, is essential for transition from intracellular persistence of Burkholderia cenocepacia to acute pro-inflammatory infection, in PLOS Pathogens, 14(12), e1007473-e1007473.
Regulation of Burkholderia cenocepacia biofilm formation by RpoN and the c-di-GMP effector BerB
Fazli Mustafa, Rybtke Morten, Steiner Elisabeth, Weidel Elisabeth, Berthelsen Jens, Groizeleau Julie, Bin Wu, Zhi Boo Zhao, Yaming Zhang, Kaever Volkhard, Givskov Michael, Hartmann Rolf W., Eberl Leo, Tolker-Nielsen Tim (2017), Regulation of Burkholderia cenocepacia biofilm formation by RpoN and the c-di-GMP effector BerB, in MicrobiologyOpen, 6(4), e00480-e00480.
Use of Synthetic Hybrid Strains To Determine the Role of Replicon 3 in Virulence of the Burkholderia cepacia Complex
Agnoli Kirsty, Freitag Roman, Gomes Margarida C., Jenul Christian, Suppiger Angela, Mannweiler Olga, Frauenknecht Carmen, Janser Daniel, Vergunst Annette C., Eberl Leo (2017), Use of Synthetic Hybrid Strains To Determine the Role of Replicon 3 in Virulence of the Burkholderia cepacia Complex, in Applied and Environmental Microbiology, 83(13), e00461-17.
NtrC-dependent control of exopolysaccharide synthesis and motility in Burkholderia cenocepacia H111
Liu Yilei, Lardi Martina, Pedrioli Alessandro, Eberl Leo, Pessi Gabriella (2017), NtrC-dependent control of exopolysaccharide synthesis and motility in Burkholderia cenocepacia H111, in PLOS ONE, 12(6), e0180362-e0180362.
Membrane vesicle-mediated bacterial communication
Toyofuku Masanori, Morinaga Kana, Hashimoto Yohei, Uhl Jenny, Shimamura Hiroko, Inaba Hideki, Schmitt-Kopplin Philippe, Eberl Leo, Nomura Nobuhiko (2017), Membrane vesicle-mediated bacterial communication, in The ISME Journal, 11(6), 1504-1509.
High intracellular c-di-GMP levels antagonize quorum sensing and virulence gene expression in Burkholderia cenocepacia H111
Schmid Nadine, Suppiger Angela, Steiner Elisabeth, Pessi Gabriella, Kaever Volkhard, Fazli Mustafa, Tolker-Nielsen Tim, Jenal Urs, Eberl Leo (2017), High intracellular c-di-GMP levels antagonize quorum sensing and virulence gene expression in Burkholderia cenocepacia H111, in Microbiology, 163(5), 754-764.

Collaboration

Group / person Country
Types of collaboration
Markus Aebi, ETH Zürich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Thomas Neu, Helmholtz Centre for Environmental Reasearch, Magdeburg, Germany Germany (Europe)
- Exchange of personnel
Tim Tolker-Nielsen, University of Copenhagen Denmark (Europe)
- Exchange of personnel
Urs Jenal, Forschungszentrum Universität Basel Switzerland (Europe)
- Publication
Burkhard Hense, Helmholtz Zentrum München, Germany Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results

Communication with the public

Communication Title Media Place Year
New media (web, blogs, podcasts, news feeds etc.) Vesicle formation through bubbling cell death in Bacillus subtilis Internet International 2017

Associated projects

Number Title Start Funding scheme
143773 Analysis of the quorum sensing circuitry of Burkholderia cenocepacia H111: The role of the Burkholderia diffusible signal factor (BDSF) 01.01.2013 Project funding (Div. I-III)
192800 The role of vesicle formation in biofilm development 01.06.2020 Project funding (Div. I-III)
154430 Investigations on the obligate leave nodule symbiosis 01.01.2015 Sinergia
192800 The role of vesicle formation in biofilm development 01.06.2020 Project funding (Div. I-III)

Abstract

In nature bacteria exist predominantly as surface-associated multispecies biofilms. While most biofilms are beneficial or even essential they can also cause problems in industrial settings or in the clinic, as persistent and chronic infections are often intrinsically linked with the formation of biofilms. Moreover, bacteria living in biofilms are much more resistant to antibiotics than planktonic cells. Biofilm cells are completely embedded in a complex matrix composed of polysaccharides, proteins, and nucleic acids, which not only keeps the cells in close contact to each other but also is diffusion barrier. Hence, biofilms represent ideal environments for small molecule mediated cell-to-cell communication, referred to as quorum sensing (QS). While work of the past years has demonstrated that QS plays an important role in biofilm formation in many bacteria, knowledge on the underlying molecular mechanisms is scarce. The present proposal aims at elucidating the importance of QS in biofilm formation in two model organisms, Burkholderia cenocepacia H111 and Pseudomonas putida IsoF. We will use B. cenocepacia H111 as a model to visualize the temporal and spatial expression patterns of different biofilm matrix components, including two polysaccharides, the large surface protein BapA and the BclACB lectins. We are particularly interested to unravel the role of the RpfFR QS system, which relies on the fatty acid signal cis-2-dodecenoic acid (BDSF), and of the downstream secondary messenger c-di-GMP in the expression of matrix components. We will use the other model organism, P. putida IsoF, to uncover the QS-dependent production of the biosurfactant putisolvin and to analyse how this molecule affects biofilm formation. We will also use this strain to investigate fundamental questions of bacterial cell-to-cell communication, namely under which conditions QS is truly used for neighbor communication to regulate expression of common goods as the QS paradigm would suggest, and when QS is only used for self-communication to control the expression of asocial traits.The proposed project is expected to significantly increase our knowledge of the mechanisms and signal transduction pathways that underlie biofilm formation. This may allow to develop novel strategies for the avoidance, eradication and manipulation of biofilms.
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