Project

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Learning from predatory bacteria: from ‘omics’ to molecular mechanisms

Applicant Huwiler Simona
Number 193401
Funding scheme Ambizione
Research institution Abteilung Mikrobiologie Institut für Pflanzenbiologie Universität Zürich
Institution of higher education University of Zurich - ZH
Main discipline Molecular Biology
Start/End 01.06.2021 - 31.05.2025
Approved amount 1'016'448.00
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All Disciplines (4)

Discipline
Molecular Biology
Genetics
Biochemistry
Experimental Microbiology

Keywords (5)

predatory bacterium; Bdellovibrio bacteriovorus; molecular mechanisms; proteomics; metabolomics

Lay Summary (German)

Lead
Das räuberische Bakterium Bdellovibrio bacteriovorus tötet bestimmte krankheitserregende Bakterien. Es wird untersucht, welche Proteine wann im räuberischen Lebenszyklus in grösserer Zahl präsent sind, um Anhaltspunkte für deren Funktion zu finden. Für einige prominent vorhandene Proteine der letzten Phase des räuberischen Lebenszyklus` sollen die molekularen Mechanismen erforscht werden.
Lay summary

B. bacteriovorus tötet bestimmte krankheitserregende Bakterien indem es in diese eindringt und sich darin fortpflanzt. Insbesondere der Prozess am Ende in welchem der Räuber die Beutereste verlässt und dabei die Beute-Zellwand und äussere Membran durchdringt, ist wenig erforscht.

Das Projekt will von räuberhaften Bakterien lernen. Durch die Nutzung von umfassenden ‘OMICS’ Technologien (Proteomics & Metabolomics) soll mehr über die molekularen Mechanismen dieses Räubers in Erfahrung gebracht werden, insbesondere in der letzten Phase des räuberischen Lebenszyklus` in welcher der Räuber die Beutereste wieder verlässt. Ein Einblick in die Mechanismen in dieser Phase soll unter anderem mit Hilfe von strukturellen und Protein-Interaktions-Studien erlangt werden.

Rund ein Drittel der Proteine des räuberischen Bakteriums B. bacteriovorus üben eine bis jetzt unbekannte Funktion aus. Einblicke in den räuberischen Lebenszyklus und insbesondere in dessen letzte Phase könnte neue oder modifizierte molekulare Mechanismen aufdecken, welche der Räuber braucht, um die Beute zu manipulieren und/oder die Beute-Hülle zu beschädigen. Diese könnten von Interesse sein, um mögliche neue Medikamente gegen Gram-negative krankheitserregende (antibiotika-resistente) Bakterien zu finden.

Direct link to Lay Summary Last update: 31.05.2021

Responsible applicant and co-applicants

Employees

Associated projects

Number Title Start Funding scheme
183896 Key signals and effects in the prey exit process of predatory bacterium Bdellovibrio bacteriovorus 01.08.2019 Postdoc.Mobility
194432 Molecular mechanisms in the prey exit process of pathogen-predator Bdellovibrio bacteriovorus 01.02.2021 Return CH Postdoc.Mobility

Abstract

Gram-negative bacterium Bdellovibrio bacteriovorus raises hope as an alternative to antibiotics and is prevalent in the environment. It serves as a model organism for predatory bacteria that invade other Gram-negative prey bacteria and replicate in their periplasm. Many processes in the predatory life cycle are enigmatic, especially in the last exit phase, where predator progeny exit the largely depleted prey cell crossing the prey’s cell wall and outer membrane.This research project aims to learn from predatory bacteria through state-of-the-art ’omics’ approaches, proteomics as well as metabolomics, covering the whole predatory life cycle with a focus on the underexplored last exit phase. This will inform current and future hypotheses investigating the complex bi-cellular predatory interactions and help identify factors involved on the molecular level. This study pursues to unravel the molecular mechanism involved in the release process of predator progeny by characterising one to two critical components in this phase where the prey bacterial cell envelope is damaged.Separation of the intracellular predatory bacterium from the bacterial prey cell will enable a highly sensitive proteomic study (collaboration with Dr. B. Roschitzki, Functional Genomics Centre Zurich, and Dr. G. Pessi and Prof. L. Eberl, University of Zurich). Metabolomics will be conducted over the whole predatory life cycle, assumed steady-state conditions can be detected in B. bacteriovorus cells that were isolated from prey during the time course of the predatory life cycle (collaboration with Prof. N. Zamboni, ETHZ). Further, metabolites that are released into the environment when the predator progeny escape the prey cell remnants will be identified. The resulting data will enable detection of the most critical components involved in the release of predator progeny cells in the exit process. The molecular mechanism of important factors will be investigated by deletion mutagenesis, localization and protein interaction studies as well as structure determination (the later with Dr. A. L. Lovering, University of Birmingham, UK).The holistic ‘omics’ approach, allows an unprecedented detailed view on the predatory life cycle of a periplasmic predatory model organism. This advances investigation of the complex predator-prey interaction at large and specifically tackling the question how the predator deconstructs the prey it has entered and what it recycles or releases in killing it. Insights into crucial processes in the exit phase will be gained. This could reveal novel or modified molecular mechanisms used by the predator to manipulate and/or damage the prey cell envelope, which are of potential interest for new drugs acting against Gram-negative bacteria or as biotechnological tools.
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