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Phages within bacteria: how resident prophages shape bacteriophage treatment
Secondary Supervisor(s): Dr Hasan Yesilkaya
University of Registration: University of Leicester
BBSRC Research Themes:
Project Outline
Most bacteria, including those that cause disease, carry phage genomes called prophages integrated within their chromosomes. These resident phages can alter bacterial fitness, virulence, physiology and susceptibility to other phages that their host encounters. Surprisingly, however, most assessments of therapeutic phages largely ignore this aspect of treatment and do not consider how resident prophages might interact with incoming phages. We have identified an unusual natural system in a clinical Klebsiella pneumoniae strain with two prophage like elements that are induced by some external phages but not others. This provides an excellent starting model, alongside other suitable prophage-host systems, to investigate how resident phages influence therapeutic phage infection.
The student will determine how prophages alter phage infection, bacterial phenotype and the evolutionary outcome of treatment. Sequencing and electron microscopy will be used to characterise selected prophage systems and the particles they produce. Isogenic bacterial strains carrying different prophage complements will be created and challenged with diverse panels of lytic phages from the Becky Mayer Centre collection. Plate-based assays, plaque assays, adsorption measurements and one-step growth experiments will quantify how prophage status changes bacterial susceptibility, phage replication and bacterial survival.
Repeated phage exposure will then test whether resident prophages alter the routes by which bacteria evolve resistance and whether this produces trade-offs in growth, capsule, metabolism or virulence. Whole-genome sequencing and targeted gene-expression experiments will identify underlying mechanisms, while computational prophage analysis across wider bacterial collections will test how general these relationships are. The project will reveal an overlooked layer of phage interaction biology and establish broa principles for understanding and selecting reliable phage treatment.
