Exploring Future Antimicrobials: Phage Tail Proteins and Bacteriocins to target Klebsiella pneumoniae

This thesis investigates two classes of proteins, phage TSPs and bacteriocins, and explores their potential as future alternatives as opposed to broad spectrum antibiotics against Klebsiella pneumoniae and related pathogenic species. First, phage-derived tail spike depolymerases targeting K1 and K2 capsules were structurally and biochemically characterised, revealing determinants of capsule specificity and enzymatic mechanism. Second, population-scale genomic analyses of a regional clinical dataset were used to characterise bacteriocin and immunity protein diversity, predict isolate-level susceptibility, and simulate bacteriocin cocktails. Together, this work provides a structural and genomic framework for developing next-generation protein therapeutics against antimicrobial-resistant Klebsiella infections.