Engineered peptide immunotherapies for the targeted disruption of Pseudomonas aeruginosa biofilms.

MR deaths have been predicted to rise to up to 10 million/year by 2050. Conversely, the development of new antimicrobials has declined: a recent WHO report warns of an inadequate antibiotic pipeline. Bacteria growing as biofilms display dramatically increased resistance to antimicrobials (x10-100), contributing significantly to AMR development.It is therefore integral that we develop new antimicrobials which target antimicrobial resistant, biofilm-forming bacteria. The overall project aim is to develop a “Paint-and-Destroy” protein-based therapeutic candidates targeting Pseudomonas aeruginosa infections. Specifically, our candidates will facilitate targeted destruction of recalcitrant Pseudomonas aeruginosa-dominant biofilms by human immune cells (macrophages). In this feasibility project, we will attach immune-activating peptides to our existing Pseudomonas-targeting protein, creating chimeric candidates. We will test the ability of these chimeras to specifically recruit macrophages to labelled P. aeruginosa for phagocytic “destruction”. Chimera efficacy will be assessed against planktonic and mono/polymicrobial biofilm cultures comprising clinical P.aeruginosa isolates.