Antibiofilm strategies for combating invasive disease caused by filamentous fungi

摘要

Introduction: Biofilms formed by filamentous fungi are recognized as a contributing factor in the virulence of invasive fungal disease, particularly aspergillosis. Furthermore, there is growing concern that, because of their inherent resistivity to systemic antifungal treatments, biofilms are contributing to increased antimicrobial resistance. Biofilm formation is naturally linked to surfaces; after all, the processes of attachment and spreading on surfaces are key steps before the first colonisers can begin to establish protective extracellular matrix. Therefore, for developing novel biomaterials, there is opportunity to investigate surface coatings that prevent surface attachment and stop fungal biofilms before they can take hold. We hypothesize that surface coatings can be engineered to eliminate or greatly reduce key biological processes in fungal cell development on surfaces, leading to promising materials in the fight against life threatening fungal disease. Materials and Methods: We have developed a coating strategy for biomaterials that uses deposition of a polymer interiayer to coat different material substrata. This layer was used as a conjugation platform for presenting bioactive agents. The effect on filamentous fungi (AspBrgillus spp.) was evaluated using biological assays and live cell imaging. The biological effects seen on the surface coatings were linked to the chemical properties of the polymer layer through detailed surface analysis. Results and Discussion: Surface coatings prepared with the attached drug caspofungin were effective in delaying spore germination and retarding hyphal development of Aspergillus fumigatus. The choice of coating strategy and human cell compatibility suggests potential use as coatings for implantable biomaterials. Conclusion: Surface coatings displaying fungistatic effects were shown to be an effective strategy for inhibiting Aspergillus growth on surfaces. The way in which these fungi experience these surface coatings, in particular during the key processes of spore germination and hyphal growth, provides a unique insight into new surface-mediated mechanisms of action. We see this platform as a useful tool to further investigate ways to combat the virulence of invasive fungal species.