Investigating the Potential of Bacteriophage Proteins Kil and NinH as Novel Antibacterials

Antibiotic resistance is a significant global health concern caused by the misuse and overuse of the existing repertoire of drugs. To combat this growing problem, alternative approaches to treat the rise of antibiotic resistant pathogenic bacteria are required. Bacteriophages, used for phage therapy to treat infections themselves, and the proteins they encode are a potential source of novel antibacterials. Embedded within these phage genomes are short polypeptides, called Kil proteins, that all appear to impact bacterial viability by blocking cell division. FtsZ, involved in Z-ring formation and essential for bacterial cell division, is known to be a target for at least some of these Kil proteins. Another gene product of interest, from bacteriophage λ, is NinH, which has DNA binding and bending properties and can also induce detrimental cell filamentation. It shares sequence and functional similarities with Fis, a bacterial nucleoid-associated protein, which plays a role in chromosome condensation, transcriptional regulation and phage site specific integration/excision reactions. In this thesis, I have studied the toxicity of Kil proteins expressed in Escherichia coli, examined their predicted structures and potential for interactions with FtsZ. I have also attempted to further understand the function of NinH and its negative effects on E. coli cell morphology. Both the Kil and NinH proteins have potential in helping to combat antibacterial resistance through novel mechanisms of cell toxicity.