Each year, over 750,000 people suffer from an invasive candidiasis infection. The most common fungal species involved in these is Candida albicans (C. albicans), with Candidaemia incurring a mortality rate of >50 % (1). Biomaterial implants are a significant contributing factor to invasive candidiasis because yeasts readily colonise implanted materials forming difficult to eradicate biofilms.
Treating infections arising from fungal biofilms on biomaterials surfaces is a clinically challenging problem. Here we report an approach comprising the covalent binding of the antifungal drug caspofungin onto the surface of biomaterials (2). Such non-releasing surface coatings should exhibit longer-lasting antifungal action against fungal cells contacting the surface, resulting in a potential disruption and prevention of fungal biofilm formation.
We have previously reported that coatings of surface-grafted caspofungin are highly effective, inhibiting Candida spp. fungal biofilm growth while not causing toxicity to human cells (> 106 yeast killing). However, the mechanism behind how caspofungin inhibits Candida spp. on surfaces is an active area of interest. Caspofungin is an echinocandin antifungal drug that inhibits the enzyme (1,3)-β-D-glucan synthase, disrupting the integrity of the fungal cell wall (3). With surface coatings we address the question of whether the surface-grafted caspofungin molecules act via the specific molecular pathway of enzyme inhibition or possibly via a nonspecific route such as membrane disruption. We have studied antifungal susceptibilities on surface coatings using a static biofilm assay for a series of C. albicans mutants and clinical isolates with varying sensitivities to caspofungin.
We found that caspofungin-resistant C. albicans mutants CA-MT441, CA-MT468, and clinical isolate CA42 were able to form biofilms on caspofungin surface coatings. Caspofungin-sensitive C. albicans strains CA-MT455, CA-MT453 and clinical isolate CA40 had no colony growth on caspofungin coatings.
Importantly, we show the mechanism of action of our surface-grafted caspofungin coating to be specific enzyme-inhibiting in nature, occurring upon contact between fungal cells and the biomaterial surface. This sheds light on a potentially industrially-viable solution to the problem of fungal biofilms on materials surfaces. Future in-vivo testing in a mouse animal model would provide us with greater insight into the antifungal activity of our coating.