Genome segregation in bacteria: investigating protein dynamics and mechanisms in the cell at single molecule level

Lead Research Organisation: University of York
Department Name: Biology

Abstract

Bacterial multidrug resistance is a global burden on human health worldwide.
Large, low copy number plasmids responsible for antibiotic resistance have
evolved strategies to ensure their faithful distribution at cell
division. Multidrug resistance plasmids harbour their own survival system, a

partition cassette, which ensures an accurate segregation of the plasmids at
cell division. When this system malfunctions, the plasmid is not stably
inherited and is ultimately lost causing bacteria to become sensitive to
antimicrobials. The multidrug resistance plasmid TP228 replicates at low
copy number in Escherichia coli. Its partition cassette encodes two proteins:
ParF, an ATPase, and ParG, a DNA-binding protein that associates to a
specific site on the plasmid. By using super-resolution microscopy on live
cells, we have shown that ParG-plasmid complexes are entrapped within a
three-dimensional ParF meshwork that assembles through the volume of the
bacterial chromosome. When the ParG protein is defective, the ParG-plasmid
complex is excluded from the chromosome volume and lost at the following
cell division. We have proposed a Venus flytrap model as a mechanism for
plasmid segregation (1).
This project will investigate the localization of ParFG-plasmid complexes in
the cell and the dynamics of complex formation at single molecule level to
shed light on the mechanistic details underpinning plasmid segregation.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/T007222/1 01/10/2020 30/09/2028
2444263 Studentship BB/T007222/1 01/11/2020 31/10/2024 Joseph John McGrory