Precision-targeting of pathogens using bacteriophage and antimicrobial peptides

Salmonellosis is a major food-borne pathogen worldwide, frequently associated with contaminated poultry and eggs. Salmonella Infantis (SI) is the 4th most common serotype in human infections in the EU, and the most frequent serotype in broiler chickens. Worryingly, multidrug-resistant isolates are increasingly common in Europe, particularly those which have acquired a pESI megaplasmid encoding resistance to multiple classes of antibiotics as well as virulence genes and enhanced tolerance of heavy metals and biocides. Alternative approaches to controlling antimicrobial resistance in Salmonella and other pathogens are urgently needed.
Two such approaches are biological control using viruses which specifically target bacteria (bacteriophages) and antimicrobial peptides (AMPs). Both approaches have unique advantages over antibiotics. Bacteriophage are self-replicating and self-limiting - reproducing only when susceptible bacteria are present. Unlike broad-spectrum antibiotics, they target a specific genus, species or strain of bacterium, avoiding potentially harmful dysbiosis in the patient.
AMPs form the basis of effective innate immune responses to bacteria and other micro-organisms in all classes of life. The most common mode of action of these to bacterial cells is thought to be via a destabilisation of the bacterial cell membrane resulting in cell lysis. AMPs can vary in size from less than 10aas to 60-70aas, their small size enabling rapid diffusion, and penetration/destabilisation of bacterial biofilms.
In this project we aim to combine the strengths of both approaches to control SI, with the ultimate aim of using this combination therapy in poultry, and potentially as a model for use in human medicine.
The PhD study is divided into two strands:
1. Isolation and characterisation of antimicrobial peptides (AMPs) specifically targeting SI.
Next Generation Peptide Phage Display (NGPD) will be used to isolate or modify peptides specifically targeting the surface of...