Functional and Structural Insights into Novel Bacteriophage Defence Islands
Year: 2021
Type: dissertation
Abstract: Bacteriophages are the most abundant organisms on the planet and are a major driving force in \nbacterial evolution. As obligate intracellular parasites, phages are reliant on their bacterial host \nfor propagation, but bacteria have evolved means to prevent phage infections. Bacteriophage \nexclusion (BREX) is a novel phage-resistance system that confers resistance to a wide array of \nphages, functioning independently of restriction-modification, CRISPR-Cas and abortive \ninfection mechanisms. BREX loci are present in ~10% of bacterial and archaeal genomes, \nincluding pathogenic strains such as non-typhoidal invasive Salmonella enterica and multidrug \nresistant Escherichia fergusonii. \nWhilst investigating the mechanism of BREX in E. fergusonii, a putative endonuclease was \ndiscovered, clustered within the BREX locus. This enzyme, BrxU, was biochemically and \nstructurally characterised, and shown to be a standalone phage defence system that targets \nmodified phage genomes. It became clear that the BREX and BrxU phage defence systems \nwere organised into a phage defence island, constituting a bacterial immune system capable of \nresisting multiple phage types. \nBoth systems detailed in this thesis represent novel antiphage mechanisms with potential for \nbiotechnological application. The BrxU endonuclease structure has been solved to 2.12 Å and \nreveals insight into key protein domains implicated in type IV restriction enzymes. BrxU has \nbeen observed to utilise a range of nucleotide and metal cofactors and confers extensive \nprotection to its bacterial host against phage infection. \n
Author: PICTON, DAVID,MARK
Language: English
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W6981930927