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The role of vesicle formation in biofilm development

English title The role of vesicle formation in biofilm development
Applicant Eberl Leo
Number 192800
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 01.06.2020 - 31.05.2024
Approved amount 1'008'000.00
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All Disciplines (2)

Discipline
Experimental Microbiology
Molecular Biology

Keywords (6)

Burkholderia cenocepacia; eDNA; biofilm matrix; Pseudomonas putida; membrane vesicle; antibiotic resistance

Lay Summary (German)

Lead
In der Natur existieren Bakterien überwiegend in oberflächenassoziierten Gemeinschaften, die als Biofilme bezeichnet werden. Biofilme können Infektionen verursachen, die zu chronischen Entzündungen und Gewebeschäden führen. Biofilminfektionen sind schwer zu behandeln, da Bakterien in Biofilmen nicht nur der Immunantwort des Wirts standhalten, sondern im Vergleich zu planktonischen Zellen wesentlich resistenter gegenüber Antibiotika sind. Daher sind neue Ansätze zur Auflösung und Bekämpfung von Biofilmen dringend erforderlich.
Lay summary

Für die Entwicklung von Anti-Biofilm-Wirkstoffen ist ein besseres Verständnis der Biofilm-Matrix erforderlich, in die die Biofilmzellen vollständig eingebettet sind. Die Matrix, die aus Polysacchariden, Lipiden, Proteinen und extrazellulärer DNA (eDNA) besteht, kreiert Diffusionsgradienten, die verschiedene Mikrohabitate erzeugen. Die erhöhte Widerstandsfähigkeit von Biofilmzellen gegen Stress ist eine Folge von metabolischen Anpassungen an die Biofilmnischen sowie von Matrixbestandteilen ist, die toxische Verbindungen neutralisieren oder deren Diffusion in den Biofilm behindern.

Die molekularen Mechanismen der eDNA-Freisetzung, seine Rolle bei der Aufrechterhaltung der strukturellen Integrität der Matrix und seine Funktion zum Schutz der Zellen ist weitgehend unerforscht. Arbeiten der letzten Jahre haben gezeigt, dass die Freisetzung von eDNA mit der Produktion von Membranvesikeln (MVs) zusammenhängt, die wichtige, jedoch völlig übersehene Bestandteile der Biofilmmatrix darstellen. Das Projekt zielt darauf ab, Wissenslücken zur Produktion und Bedeutung von eDNA und MVs in Biofilmen zu schließen, wodurch ein wichtiger Beitrag zur Entwicklung neuartiger Therapiestrategien für die Behandlung von Biofilminfektionen geleistet wird.


Direct link to Lay Summary Last update: 28.05.2020

Responsible applicant and co-applicants

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Associated projects

Number Title Start Funding scheme
186410 A New Class of Signal Molecules in Bacteria: Data-Driven Discovery, Mechanism, and Biological Function (Signalin’Bac) 01.10.2019 Sinergia
169307 Communication in bacterial biofilms 01.01.2017 Project funding (Div. I-III)
169307 Communication in bacterial biofilms 01.01.2017 Project funding (Div. I-III)

Abstract

In most natural habitats, bacteria form surface-associated multispecies consortia, referred to as biofilms. While most biofilms are beneficial and in some cases even essential, they can cause biocorrosion in industrial settings and persistent and chronic infections in humans. They are considered particularly problematic in the clinic, as biofilm infections are difficult to treat because bacteria growing in biofilms withstand host immune responses and are much more resistant to antibiotics compared to planktonic cells. The production of a matrix, consisting of polysaccharides, lipids, proteinaceous constituents and extracellular DNA (eDNA), is thought to be responsible for many phenotypes associated with sessile cells, including high levels of resistance and low metabolic activity due to nutrient diffusion limitation. Most research on matrix material has focussed on polysaccharides and proteins and some insights on the role of eDNA for biofilm stability and resistance has been gained in the past few years. However, the mechanisms responsible for eDNA release are controversially discussed in the field. Recent work has identified explosive cell lysis, which depends on stress-induced expression of phage-derived holin/endolysin systems, as a novel mechanism of eDNA release. This process also generates bacterial membrane vesicles (MVs), which are highly abundant, yet entirely overlooked components of the biofilm matrix. Hence, eDNA release, MV production and biofilm formation appear to be intrinsically linked and this hypothesis will be rigorously tested within this project. Using high-end microscopy techniques combined with various fluorescent stains we will monitor the spatial and temporal biosynthesis of matrix components and investigate how eDNA and MVs influence antibiotic resistance, DNA transfer, bacterial killing and the release of bioactive compounds. The specific aims of this project are to i) characterize the structures and compositions of MVs produced in planktonic culture and biofilms, ii) define the SOS response and its role in MV and eDNA release, iii) to unravel the role of biosurfactants in MV and nanotube formation, iv) to investigate the biological functions of MVs and eDNA in biofilms and v) to visualize eDNA and MVs within the biofilm matrix and identify possible interaction partners. The proposed project will increase our current knowledge of the function of eDNA and MVs in biofilms, which will provide us with a solid framework to develop innovative strategies for the avoidance, eradication and manipulation of biofilms. Moreover, a detailed understanding of the underlying mechanisms of MV biogenesis will open novel avenues for the production of tailored MVs for medical and biotechnological applications.
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