Adhesion to host cell membrane microdomains in cornea as an antimicrobial target to prevent corneal ulceration

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"We are proposing to add significant value to the drug target validation by: i) Identification of the lead peptide: using in vitro assays to select the peptide with the widest therapeutic window prior to the main work packages. ii) Evaluation of the therapeutic potential of the peptide: determining if treatment will be prophylactic only, or if peptide can be used as a treatment for more established infections. iii) Evaluation of the effects of peptide treatment on biofilm infections: the biofilm work package will be brought forward to determine if the most highly resistant infections
can be treated with peptide alone or in combination with conventional antibiotics. iv) Developing a global microbial keratitis network: to broaden the use of peptide treatment beyond UK and India, we will identify and evaluate potential partners in other LMIC such as China, Egypt, Iraq and Kenya, arranging preliminary meetings with clinicians and researchers and organising a conference to bring the partners together to develop a keratitis strategy. v) Preliminary testing of passive immunisation as a strategy to complement peptide treatment. We will work with a contract research organisation in Nepal to investigate the potential of naturally occurring antibacterial immunoglobulins in cows’ milk that should provide an inexpensive source of antiinflammatory, anti-adhesive antibodies. These will be tested alone and in combination with peptide on corneal explant cultures."