To defend or to offend? : Bacterial defence and competition systems

• Bacteria are prokaryotic microorganisms that can be found in all niches of the biosphere. Bacteria must constantly evolve in order to survive and adapt to their environments. Defence systems and competition systems play a vital role in ensuring the survival of bacteria. The projects included in this thesis aim to further understand how these systems function, as well as adapting them in order to design probiotic strains with built-in biocontainment mechanisms. In paper I, we investigate how internal expression of Rearrangement hotspot (Rhs) toxins allows protection against Rhs toxin delivery in S. Typhimurium. In paper II, we examine bacterial competition systems found in enterotoxigenic E. coli (ETEC) strains and explore the evolution of toxin arsenals within ETEC family lineages. In paper III, we develop a fluorescence flow cytometry-based high-throughput screening method and apply it to isolate a highly competitive commensal E. coli strain that possesses a diverse arsenal of competition systems. In paper IV, we design and construct a synthetic CRISPR system that is able to protect E. coli from acquisition of antibiotic resistance genes through horizontal gene transfer. The work presented in this thesis contribute to our understanding of the functions of bacterial defence and competition systems, at the same time, laying the groundwork for how these systems can be studied in a high-throughput manner as well as how they can be adapted in the future to design synthetic microbial strains with clinical and environmental applications.

Nyckelord

bacterial defence systems; bacterial competition systems; toxin-antitoxin systems; colicin; contact-dependent growth inhibition (CDI); type VI secretion system (T6SS); Rearrangement hotspot (Rhs) proteins; CRISPR; horizontal gene transfer; antibiotic resistance; Salmonella; Enterotoxigenic E. coli (ETEC); probiotics; synthetic biology.

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