Exploitation of the antifungal and antibiofilm activities of plumbagin against Cryptococcus neoformans

Abstract

Cryptococcus neoformans is an important opportunistic fungal pathogen that causes various infections. Here, the antifungal and antibiofilm activities of plumbagin against C. neoformans and the underlying mechanisms were evaluated. The minimum inhibitory concentration (MIC) of plumbagin against C. neoformans H99 was 8 μg ml⁻¹. Plumbagin disrupted the cell membrane integrity and reduced the metabolic activities of C. neoformans H99. C. neoformans H99 biofilm cells were damaged by plumbagin at a concentration of 64 μg ml⁻¹, whereas 48-h mature biofilms were dispersed at a plumbagin concentration of 128 μg ml⁻¹. Whole-transcriptome analysis of plumbagin-treated C. neoformans H99 in the biofilm and planktonic states identified differentially expressed genes enriched in several important cellular processes (cell membrane, ribosome biogenesis, fatty acid synthesis, melanin and capsule production). Notably, plumbagin damaged biofilm cells by downregulating FAS1 and FAS2 expression. Thus, plumbagin can be exploited as an antifungal agent to combat C. neoformans-related infections.

Keywords:

• Cryptococcus neoformans
• plumbagin
• antifungal
• antibiofilm
• transcriptome

Additional information

Funding

This work was supported partly by the National Natural Science Foundation (11975177), the Science and Technology Plan Project of Xianyang Science and Technology Bureau (2021ZDYF-NY-0007), and Natural Science Pre-research Fund of Shaanxi University of Science and Technology (2017BJ-48).