Antifungal and Antibiofilm Efficacy of Paeonol Treatment Against Biofilms Comprising Candida albicans and/or Cryptococcus neoformans

Abstract

Fungal populations are commonly found in natural environments and present enormous health care challenges, due to increased resistance to antifungal agents. Paeonol exhibits antifungal activities; nevertheless, the antifungal and antibiofilm activities of paeonol against Candida albicans and Cryptococcus neoformans remain largely unexplored. Here, we aimed to evaluate the antifungal and antibiofilm activities of paeonol against C. albicans and/or C. neoformans (i.e., against mono- or dual-species). The minimum inhibitory concentrations (MICs) of paeonol for mono-species comprising C. albicans or C. neoformans were 250 μg ml−1, whereas the MIC values of paeonol for dual-species were 500 μg ml−1. Paeonol disrupted cell membrane integrity and increased the influx of gatifloxacin into cells of mono- and dual-species cells, indicating an antifungal mode of action. Moreover, paeonol at 8 times the MIC damaged mono- and dual-species cells within C. albicans and C. neoformans biofilms, as it did planktonic cells. In particular, at 4 and 8 mg ml−1, paeonol efficiently dispersed preformed 48-h biofilms formed by mono- and dual-species cells, respectively. Paeonol inhibited effectively the yeast-to-hyphal-form transition of C. albicans and impaired capsule and melanin production of C. neoformans. The addition of 10 MIC paeonol to the medium did not shorten the lifespan of C. elegans, and 2 MIC paeonol could effectively protect the growth of C. albicans and C. neoformans-infected C. elegans. Furthermore, RNA sequencing was employed to examine the transcript profiling of C. albicans and C. neoformans biofilm cells in response to 1/2 MIC paeonol. RNA sequencing data revealed that paeonol treatment impaired biofilm formation of C. albicans by presumably downregulating the expression level of initial filamentation, adhesion, and growth-related genes, as well as biofilm biosynthesis genes, whereas paeonol inhibited biofilm formation of C. neoformans by presumably upregulating the expression level of ergosterol biosynthesis-related genes. Together, the findings of this study indicate that paeonol can be explored as a candidate antifungal agent for combating serious single and mixed infections caused by C. albicans and C. neoformans.

Metabolomic profiles of the liquid state fermentation in co-culture of Eurotium amstelodami and Bacillus licheniformis

“…Glycerophospholipids are important components of cell membranes ( Sohlenkamp and Geiger, 2016 ; Qian et al, 2022 ). Previous studies have shown that glycerophospholipid metabolism plays an especially important role in the response to extracellular stress ( Lopalco et al, 2017 ; Zai et al, 2017 ).…”

C-Type Natriuretic Peptide Acts as a Microorganism-Activated Regulator of the Skin Commensals Staphylococcus epidermidis and Cutibacterium acnes in Dual-Species Biofilms

“…In the beginning of this study, no analyses of the transcriptome of duals-species communities could be found in the published literature. However, during the last year, several deep and substantial studies were published with two papers dedicated to communities of Candida albicans with different bacteria ( Staphylococcus aureus [ 38 ], Streptococcus mutans [ 39 ]), one manuscript about a fungal community of C. albicans and Cryptococcus neoformans [ 40 ], and one article focused on “coaggregated” Streptococcus gordonii and Fusobacterium nucleatum in mixed pellets, i.e., not in actual biofilm [ 39 ]. Interkingdom communities seem to be easier to analyze; however, in the streptococci-fusobacteria community, there was also a good correlation in results.…”

“…Short et al [ 38 ] and Lu [ 39 ] et al used 16S/18S rRNA genes for C. albicans / S. aureus [ 41 , 42 ] and S. gordonii / F. nucleatum, respectively. In case of C. albicans [ 39 ] and both C. albicans and C. neoformans [ 40 ], actin-encoding act1 gene was used as a reference. Interestingly, Lu and colleagues analyzed only the transcriptome of C. albicans and no data for S. mutans were presented.…”

Protective mechanism of Paeonol on central nervous system

“…Its inhibitory effect is characterized by destroying bacterial cell membrane and blocking the biofilm structure formed on non‐biological surface (Zeng et al, 2022). Similarly, it can inhibit the formation of Candida albicans biofilm and play a therapeutic role on Candida albicans associated colitis (Ge et al, 2021; Pan et al, 2021; Qian et al, 2022). In addition, it also inhibited the expression of virulence factors of Pseudomonas aeruginosa to reduce bacterial virulence and reduce its damage to macrophages (Tang et al, 2022).…”