The Role of BrxR in Regulating Bacterial Phage-Defence Systems

Abstract

Bacteria are under constant attack by bacteriophages, their natural predators that outnumber them 10-fold. The resulting selection pressure has given rise to a diverse range of phage-defence systems within bacteria. These systems are often clustered within ‘defence islands’ in the bacterial genome, facilitating coregulation and complementary action. In this thesis, regulation of an Escherichia fergusonii defence island containing both BREX and type IV restriction modification systems by BrxR protein is explored. Through LacZ assays, mutagenesis studies, and EOP assays, BrxR is functionally characterised as a ligand-binding transcriptional repressor of phage defence. The roles of the HTH and WYL domains found within BrxR are identified as likely DNA- and ligand-binding regions, respectively, and the groundwork is laid for future study of BrxR, including identification of its cognate phage-associated ligand.