Phage Therapy and Phage Engineering technologies for tackling Antibiotic-Resistance in Bacterial Infections

In recent years, the escalating crisis of antibiotic resistance has spurred the search for alternative antimicrobial strategies, with bacteriophage therapy emerging as a promising candidate. In this thesis, we first provide a comprehensive examination of bacteriophage biology, detailing their classification into families and offering an in-depth analysis of their structural components—including the capsid, genome, and tail. We then investigate the phage life cycles, with particular emphasis on the mechanisms of genome translocation within bacterial cells and the contrasting infection strategies of the lysogenic and lytic cycles. Concluding the biology chapter, we explore the multifaceted interactions between phages and the mammalian immune system, their role in disseminating antibiotic resistance among microbial communities, and the co-evolutionary dynamics that lead to the emergence of phage resistant bacteria and related considerations. The following chapter presents a thorough review of phage therapy, outlining the critical steps required to harness phages as effective antimicrobial agents. We detail the processes of isolation, characterization, and screening, and discuss the foundational principles behind rational phage dosage, administration, and therapeutic techniques aimed at maximizing their efficacy. This discussion also highlights the inherent limitations of conventional phage therapy. Finally, the thesis examines advanced genome engineering techniques for personalized phage editing. By integrating innovative genetic modification strategies, we demonstrate how engineered phages can enhance conventional phage therapy, possibly overcoming its intrinsic limitations.