Background: MM-86553 is a new antifungal agent that inhibits the ability of C. albicans to initiate a pathogenic program that includes a morphologic transition from yeast to hyphal growth. In addition to morphologic changes, hyphal C. albicans cells attach to surfaces and become less sensitive to antifungal drugs than yeast cells. We investigated the ability of MM-86553 to potentiate the antifungal effect of Amphotericin B (AMB) against C. albicans grown on a solid surface. Methods: An inoculum of 1 x 104 CFU/well of C. albicans was grown in a flat-bottomed, polystyrene plate in 100 µL of RPMI medium for 24 hours at 37°C ± 10 µM MM-86553. A nonhyphal C. albicans riv1 mutant strain was also tested. The cultures were challenged with a serial dilution of AMB ranging from 64 µg/mL to 0.31µg/mL for 24 hours at 37°C. MICs were determined using a standard cell viability assay. Results: The AMB MIC for hyphal C. albicans cultures was >128-fold higher than that of either non-hyphal riv1 mutant cultures or of MM-86553 containing cultures. Conclusions: MM-86553 exhibits potent synergy with AMB against C. albicans grown in vitro under conditions that promote invasive hyphal growth and adherence to surfaces. As C. albicans invades tissues in a hyphal morphology and adheres to surfaces in vivo, these findings indicate that MM-86553 and other anti-invasins have important potential clinical utility as cotherapeutic agents.
Full conference title:
43rd Interscience Conference on Antimicrobial Agents
- ICAAC 43rd