Development of a novel antimicrobial therapy using synthetic phage inducible chromosomal islands (PICIs)

Studentship strategic priority area:Bacteriology and Bioengineering
Keywords:Staphylococcus, pathogenicity islands, antimicrobial resistance, microfluidics

Antibiotic resistant bacteria are observed with increasing prevalence. Alternatives to antibiotics have thus become a public health priority for the treatment of bacterial infections. Bacteriophages are capable of killing bacteria (even the antibiotic-resistant variants) as part of their natural life cycle and thus are considered one of the most promising alternatives to combating infections. However, recent studies have revealed the limitations of phage therapy e.g. in the context of the narrow host range displayed by bacteriophages or to the exponential-phage restricted effect. During the last years, we have identified and extensively characterised a novel family of pathogenicity islands, the PICIs (phage-inducible chromosomal islands). In this project we will use synthetic PICI particles as effective vectors to deliver DNA both intra and inter-species to provide a novel antimicrobial therapy. Using different strategies, these synthetic elements will be engineered to encode genes whose expression will be lethal for the targeted, recipient bacteria. Following a Trojan Horse strategy, upon activation from outside the cell, the genetic constructions introduced into the bacterial chromosome via PICI integration will trigger bacterial death from within the cell. Engineered fluidic approaches will be developed to create a high throughput characterisation and deliver systems to optimise the Trojan Horse strategy in vivo.