title: Drug susceptibility of matrix-encapsulated Candida albicans nano-biofilms.
abstract: The rise in the use of biomedical devices and implants has seen a concomitant surge in the advent of device-related nosocomial (hospital-acquired) infections of bacterial and fungal origins. The most common nosocomial fungal infection is candidiasis caused mainly by Candida albicans biofilms. Candidiasis is associated with an unacceptably high mortality rate, and there is an urgent need for the discovery of new antifungal drugs that prevent or control biofilm formation. To this end, we recently developed an ultra-high-throughput microarray platform consisting of nano-scale biofilms of C. albicans encapsulated in collagen or alginate hydrogel matrices for antifungal drug screening. Here, we report that the choice of matrix influences the apparent susceptibility of C. albicans to the common antifungal drugs, amphotericin B, and caspofungin. While amphotericin B is equally effective against biofilms grown in collagen and alginate matrices, caspofungin is effective only against biofilms grown only in alginate, but not in collagen. We demonstrate differences in the distribution of the drugs in the two matrices may contribute to the susceptibility of C. albicans nano-biofilms. In a larger context, our results highlight the importance of the choice of matrix as a parameter in 3D cell encapsulation, and suggest a screening strategy to predict drug performance in vivo.
authors.affiliation: Department of Biomedical Engineering, The University of Texas at San Antonio, San Antonio, Texas, 78249.
authors.forename: Anand
authors.initials: A
authors.lastname: Srinivasan
authors.forename: Celia Macias
authors.initials: CM
authors.lastname: Gupta
authors.forename: C Mauli
authors.initials: CM
authors.lastname: Agrawal
authors.forename: Kai P
authors.initials: KP
authors.lastname: Leung
authors.forename: Jose L
authors.initials: JL
authors.lastname: Lopez-Ribot
authors.forename: Anand K
authors.initials: AK
authors.lastname: Ramasubramanian
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D002176:Candida albicans / Q000187:drug effects*; D000077336:Caspofungin; D018914:Cells, Immobilized / Q000187:drug effects; D004353:Drug Evaluation, Preclinical / Q000379:methods; D054714:Echinocandins / Q000494:pharmacology; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D055666:Lipopeptides; D008826:Microbial Sensitivity Tests / Q000379:methods*
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D000666:Amphotericin B; D000077336:Caspofungin
keywords: Candida albicans; biofilms; caspofungin; drug screening; high-throughput; hydrogels; microarray