Peptide-functionalized POMs as biofilm disruption agents: searching for synergy in bactericidal materials

Description du projet

Les priver du droit de se rassembler

À l’instar d’un groupe de manifestants qui se tiennent bras dessus bras dessous pour opposer davantage de force et de résistance aux tentatives de dispersion, les bactéries forment ce que l’on appelle des biofilms dans lesquels elles adhèrent les unes aux autres par l’intermédiaire d’une matrice polymère extracellulaire collante qu’elles fabriquent elles-mêmes. Ces films les protègent contre les antibiotiques et contribuent à accroître la résistance aux antimicrobiens. Les biofilms se forment sur divers substrats, notamment les plastiques et les métaux, et sont particulièrement dangereux dans les hôpitaux où ils peuvent se former sur des éléments tels que les cathéters, les sutures ou les implants. Leurs jours sont peut-être comptés grâce aux travaux du projet PePiPOM, financé par l’UE, et aux nouveaux matériaux qui en découlent et qui empêchent l’agrégation des bactéries tout en les tuant.

Objectif

Antimicrobial resistance is an increasingly serious threat to global public health and immediate action must be taken to prevent its ever-increasing spread. One approach to overcome this problem is the development of new materials and coatings with bactericidal action; in particular those which tackle biofilm formation specifically. By inhibiting the growth of biofilms, bacteria become more sensitive to treatment and resistance diminishes. The applicant has designed PePiPOM to develop peptide-functionalized polyoxometales (POMs) that possess synergic bactericidal activity. The PePiPOM materials combine the anti-aggregation activity of POM molecules (key to tackling growth of biofilm matrix) with the bactericidal effect of POMs + antimicrobial peptides (to rupture bacterial cell membranes and/or internalise and destroy bacterial cells). Central to the success of this proposal is a novel approach for the synthesis of POM-hybrids whereby an “on-POM polymerisation” will be used to produce peptide-POM hybrids. The design of the antimicrobial peptides will also play a key role in the success of the project, since they will provide the required properties for an improved and synergistic activity. The resulting PePiPOM biofilm inhibitors will be tested for both their anti-aggregation and antibacterial activity, and the most effective candidates will be evaluated as anti-biofilm agents on plastic and metal surfaces. The fundamental academic aspects of these results will be of interest to the chemistry and microbiology communities and their application of great relevance to industry and the general public. The PePiPOM MCSA will open new research horizons for hybrid materials with synergic antimicrobial properties, but also importantly, will offer a real boost in the career development of the applicant on her route to achieving her professional career objectives.