Interactions between Campylobacters and their bacteriophages

Campylobacter jejuni is a leading cause of human bacterial enteritis worldwide. Consumption of contaminated poultry meat is considered a major source of infection. The use of virulent bacteriophages as a form of biocontrol to specifically reduce this pathogen in poultry (phage therapy) is a promising intervention that does not rely on antimicrobials and therefore circumvents the emergence of antibiotic-resistant Campylobacter strains. In order to achieve this, a better understanding of the mechanisms involved in phage-host interactions at the molecular level would assist in the development of the strategy and the selection of bacteriophages. The main objective of this study was to therefore examine such interactions between Campylobacter and its virulent phages. To achieve this, the transcriptional response of C. jejuni to phage infection was investigated, along with the role of a Type II restriction-modification system during phage infection of Campylobacter. These studies were conducted using the highly phage-sensitive Campylobacter strain, C. jejuni PT14, in conjunction with a number of group II and III bacteriophages (Eucampyvirinae). Transcriptome studies (RNA-Seq) revealed a phage-induced host response that included a demand for iron and oxygen. This was highlighted by the up-regulation of several siderophore-based iron acquisition genes and down-regulation of genes associated with a number of anaerobic electron transport pathways that utilise alternative electron acceptors to oxygen. In addition, the pattern of gene regulation also suggested apo-Fur regulation of the iron-responsive and flagellar biogenesis genes. This host response has been proposed to occur as a consequence of the reduction of ribonucleotides to form deoxyribonucleotides during phage DNA replication. This process is catalysed by the enzyme ribonucleotide reductase and requires iron and oxygen during the formation of a reactive di-iron centre within the β-subunit of the enzyme. Unusually knock-out mutants of a Type II restriction-modification system had a negative impact on phage replication. The A911_00150 mutant displayed pleiotropic changes in motility, cell based invasion and the ability to colonise chickens. Transcriptome analysis highlighted down-regulation of the genes required for the synthesis of the bacterial flagellum