Horizontal transfer of anti-viral defences between bacterial species

: (Alternative Format Thesis)

Abstract

Viruses that infect bacteria, known as bacteriophages (phages) are found wherever bacteria exist in the microbial world. The antagonistic co-evolution between host and parasite has resulted in the evolution of bacterial defence systems to protect hosts. CRISPR-Cas (clustered regularly interspaced short palindromic repeats – CRISPR associated) systems can acquire DNA from invading genetic elements such as phages and plasmids, then integrate the foreign DNA into the host genome to produce adaptive, sequence-specific, heritable immunity. Anti-viral defence systems are proposed to be frequently exchanged between bacterial hosts via horizontal gene transfer (HGT) events. However, we are lacking in experimental studies that investigate the downstream evolutionary consequences to a host of acquisition of a CRISPR-Cas system. In this thesis, I first investigated the conditions that allow spread and maintenance of a defence system. I explored whether a subpopulation with a CRISPR-Cas system can be selected for in an isogenic population lacking the defence system but with alternative resistance strategies available, using mathematical modelling and experimental work. To further understand how CRISPR-Cas systems alter bacteria-phage interactions, I created a model system to allow a synthetic CRISPR-Cas system to be transferred to the chromosome of a bacterial host. When tested against a range of phages, this revealed that the efficacy of CRISPR-Cas interference can be modulated by spacer sequence, and nutrient conditions. Next, we integrated this synthetic CRISPR-Cas DNA into a naïve host species to model a HGT event. The synthetic CRISPR-Cas system was successful in phage and plasmid resistance, as well as spacer acquisition. However, in the naïve host, productive CRISPR-Cas immunity was dependent on both environment and species, and did not result in a strong competitive advantage. Together these results suggest that the rate of HGT events are likely not the only bottleneck to the successful sharing of defence systems in microbial populations.

Date of Award	22 Jan 2025
Original language	English
Awarding Institution	University of Bath
Supervisor	Tiffany Taylor (Supervisor), Edze R. Westra (Supervisor) & Tim Rogers (Supervisor)