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Morphological plasticity of bacteria to stressful conditions

Timeline

May 2016 – May 2020

Group and collaboration

Ariane Briegel & Dennis Claessen, Leiden University
PhD student: Eveline Ultee

Promotion

Dissertation: Structural characterization of the cell envelope in Actinobacteria under changing environments

Date: 02 December 2020

Project description

Bacteria use their rigid outer layer to withstand a large variety of external stresses. This outer layer is called the cell wall: a stress-bearing structure, composed of a cross-linked network of peptidoglycan. Peptidoglycan has proven to be a successful target for antibacterial compounds and for recognition of bacterial pathogens by the host immune system. A proposed mechanism to evade these conditions and survive is the modification or even loss of the cell wall. Research has shown that bacteria can chemically convert into a wall-less or L-form state, in which the cells are able to grow and propagate without a cell wall. This process has been used in the establishment of persistent infections in pathogenic species such as Mycobacterium tuberculosis. To gain insight into the detailed characteristics of these cell-wall less states, we utilise the related, non-pathogenic Actinomycetales.

Our lab has shown that a selection of filamentous Actinomycetes species is able to spontaneously extrude wall-less bacterial cells upon exposure to hyperosmotic stress (S-cells). In order to understand the structural changes that accompany the formation of wall-less bacteria, we first need to understand the architecture of the cell wall structure of filamentous Actinomycetes itself. Studying the cell wall structure and formation and extrusion of wall-less bacteria will contribute to a better understanding of how bacteria adapt to changing environments and evade antibacterial compounds.

Tasks

  1. To study the structure of the cell wall in polar growing bacteria
    • We will use cryo-electron tomography the visualize isolated sacculi (cell wall material) of model Actinomycete Streptomyces coelicolor and compare new (cell pole) and older regions (lateral sides) of the cell wall
  2. To understand how the bacterial cell and its cell wall restructure in order to extrude wall-less bacteria.
    • We will use a combination of imaging techniques (time-lapse microscopy, (cryo-) fluorescence light and electron microscopy/tomography) to describe structural changes during the formation of wall-less bacteria
    • We will analyze the role of members of the multi-protein complex at the tip, which interacts with the peptidoglycan-synthesis machinery

Disease Intervention Strategies is the overarching theme for more than 10 PhD tracks in NCOH projects to create new interdisciplinary, inter-thematic, and inter-institutional research collaborations.

PhD student interview

Interview: ‘I will always have a soft spot for bacteria’

Understanding how bacteria adapt in order to survive is fundamentally interesting and can potentially help us to understand bacterial infections, says Eveline Ultee who researched how bacteria change their shape.

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