The potential of anti-adhesion therapy in a biofilm infection model (360G-Wellcome-211787_Z_18_Z)

In a search for alternative antibiotic therapeutic approaches, innovative strategies that aim to modulate host components essential for infection have come to prominence. Many Gram-negative and Gram-positive pathogens such as Pseudomonas aeruginosa and Staphylococcus aureus utilise host microdomains formed by the tetraspanin superfamily of transmembrane proteins as an adhesion platform and a gateway for infection. Bacterial adherence is thus considered an essential step for colonisation and infection, and in 65-80% of cases, this leads to the formation of bacterial communities (biofilms). Such infections are difficult to eradicate as biofilms provide a protective mode of growth. The project proposed herein aims to test the efficiency of a library of anti-adhesion peptides that specifically target tetraspanin-enriched microdomains in a biofilm infection model. To achieve this, an in-situ representative biofilm infection model (harbouring P. aeruginosa and/or S. aureus) will be established on the surface of human-derived skin cell lines, namely keratinocytes. Biofilm development will be analysed using the BioFlux, confocal microscopy and bacterial counting. The efficiency of tetraspanin-derived peptides will then be tested; with the aim of determining if this therapy prevents biofilm formation, disrupts existing biofilms or enhances the efficacy of conventional antibiotics. Keywords: biofilm infection model, anti-adhesives, host-pathogen interaction, tetraspanins.