Enhancement of the antibiofilm activity of amphotericin B by polyamine biosynthesis inhibitors

• Polyamine biosynthesis inhibitors can be used to enhance the activity of amphotericin B (AmB) against Candida albicans biofilms.
• Polyamine biosynthesis inhibitors can also enhance the efficacy of caspofungin, miconazole and nystatin against C. albicans biofilms.
• The combination of AmB and polyamine biosynthesis inhibitors increases reactive oxygen species levels in biofilm cells.
• The caspase pathway mediated by CaMCA1 plays an essential role in enhancing the antibiofilm efficacy of AmB by polyamine biosynthesis inhibitors.

The aim of this study was to investigate the effect of polyamine biosynthesis inhibitors on the activity of amphotericin B (AmB) against Candida albicans biofilms and to clarify the underlying mechanisms. The antibiofilm activity of AmB was significantly enhanced when used in combination with the polyamine biosynthesis inhibitors 1,4-diamino-2-butanone (DAB) and α-difluoromethylornithine (DFMO). Further study showed that DAB and DFMO also enhanced the antibiofilm activity of several other antifungal agents. Moreover, the combination of AmB and polyamine biosynthesis inhibitors resulted in an increase in intracellular levels of reactive oxygen species. In addition, caspase activity and transcription of the caspase-encoding gene CaMCA1 were greatly increased upon combined treatment with polyamine biosynthesis inhibitors and AmB. Consistently, the biofilm formed by a Δcamca1 mutant exhibited greater viability and lower caspase activity than that of the wild-type strain upon combined treatment. These data provide useful information for the development of new strategies to enhance the antibiofilm activities of antifungal agents.