Antifungal and antibiofilm activities of flavonoids against Candida albicans: Focus on 3,2′-dihydroxyflavone as a potential therapeutic agent
Ontology highlight
ABSTRACT:
SUBMITTER:
PROVIDER: S-EPMC11340609 | biostudies-literature | 2024 Jul
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:The rapid increase in the emergence of antifungal-resistant Candida albicans strains is becoming a serious health concern. Because antimicrobial peptides (AMPs) may provide a potential alternative to conventional antifungal agents, we have synthesized a series of peptides with a varying number of lysine and tryptophan repeats (KWn-NH2). The antifungal activity of these peptides increased with peptide length, but only the longest KW5 peptide displayed cytotoxicity towards a human keratinocyte cell line. The KW4 and KW5 peptides exhibited strong antifungal activity against C. albicans, even under conditions of high-salt and acidic pH, or the addition of fungal cell wall components. Moreover, KW4 inhibited biofilm formation by a fluconazole-resistant C. albicans strain. Circular dichroism and fluorescence spectroscopy indicated that fungal liposomes could interact with the longer peptides but that they did not release the fluorescent dye calcein. Subsequently, fluorescence assays with different dyes revealed that KW4 did not disrupt the membrane integrity of intact fungal cells. Scanning electron microscopy showed no changes in fungal morphology, while laser-scanning confocal microscopy indicated that KW4 can localize into the cytosol of C. albicans. Gel retardation assays revealed that KW4 can bind to fungal RNA as a potential intracellular target. Taken together, our data indicate that KW4 can inhibit cellular functions by binding to RNA and DNA after it has been translocated into the cell, resulting in the eradication of C. albicans.
| S-EPMC7285485 | biostudies-literature
Project description:Biofilms are microbial colonies that are encased in an organic polymeric matrix and are resistant to antimicrobial treatments. Biofilms can adhere to both biotic and abiotic surfaces, allowing them to colonize medical equipment such as urinary and intravenous catheters, mechanical heart valves, endotracheal tubes, and prosthetic joints. Candida albicans biofilm is the major etiological cause of the pathogenesis of candidiasis in which its unobstructed growth occurs in the oral cavity; trachea, and catheters that progress to systemic infections in the worst scenarios. There is an urgent need to discover novel biofilm preventive and curative agents. In the present investigation, an effort is made to observe the role of cyanobacteria-derived AgNPs as a new antibiofilm agent with special reference to candidiasis. AgNPs synthesized through the green route using Anabaena variabilis cell extract were characterized by UV-visible spectroscopy. The nanoparticles were spherical in shape with 11-15 nm size and were monodispersed. The minimum inhibitory concentration (MIC) of AgNPs was obtained at 12.5 μg/mL against C. albicans. AgNPs 25 μg/mL showed 79% fungal cell membrane permeability and 22.2% ROS production. AgNPs (25 μg/mL) also facilitated 62.5% of biofilm inhibition and degradation. Therefore, AgNPs could be considered as a promising antifungal agent to control biofilm produced by C. albicans.
| S-EPMC8782275 | biostudies-literature
Project description:Candida albicans is known as a commensal microorganism but it is also the most common fungal pathogen in humans, causing both mucosal and systemic infections. Biofilm-associated C. albicans infections present clinically important features due to their high levels of resistance to traditional antifungal agents. Quorum sensing is closely associated with biofilm formation and increasing fungal pathogenicity. We investigated the ability of the novel bacterial quorum sensing quencher thiazolidinedione-8 (S-8) to inhibit the formation of, and eradication of mature C. albicans biofilms. In addition, the capability of S-8 to alter fungal adhesion to mammalian cells was checked. S-8 exhibited specific antibiofilm and antiadhesion activities against C. albicans, at four- to eightfold lower concentrations than the minimum inhibitory concentration (MIC). Using fluorescence microscopy, we observed that S-8 dose-dependently reduces C. albicans-GFP binding to RAW macrophages. S-8 at sub-MICs also interfered with fungal morphogenesis by inhibiting the yeast-to-hyphal form transition. In addition, the tested agent strongly affected fungal cell wall characteristics by modulating its hydrophobicity. We evaluated the molecular mode of S-8 antibiofilm and antiadhesion activities using real-time RT-PCR. The expression levels of genes associated with biofilm formation, adhesion and filamentation, HWP1, ALS3 and EAP1, respectively, were dose-dependently downregulated by S-8. Transcript levels of UME6, responsible for long-term hyphal maintenance, were also significantly decreased by the tested agent. Both signaling pathways of hyphal formation-cAMP-PKA and MAPK-were interrupted by S-8. Their upstream general regulator RAS1 was markedly suppressed by S-8. In addition, the expression levels of MAPK cascade components CST20, HST7 and CPH1 were downregulated by S-8. Finally, transcriptional repressors of filament formation, TUP1 and NRG1, were dramatically upregulated by our compound. Our results indicate that S-8 holds a novel antibiofilm therapeutic mean in the treatment and prevention of biofilm-associated C. albicans infections.
| S-EPMC4010395 | biostudies-literature
Project description:Candida biofilms are tolerant to conventional antifungal therapeutics and the host immune system. The transition of yeast cells to hyphae is considered a key step in C. albicans biofilm development, and this transition is inhibited by the quorum-sensing molecule farnesol. We hypothesized that fatty acids mimicking farnesol might influence hyphal and biofilm formation by C. albicans. Among 31 saturated and unsaturated fatty acids, six medium-chain saturated fatty acids, that is, heptanoic acid, octanoic acid, nonanoic acid, decanoic acid, undecanoic acid and lauric acid, effectively inhibited C. albicans biofilm formation by more than 75% at 2 µg ml-1 with MICs in the range 100-200 µg ml-1 . These six fatty acids at 2 µg ml-1 and farnesol at 100 µg ml-1 inhibited hyphal growth and cell aggregation. The addition of fatty acids to C. albicans cultures decreased the productions of farnesol and sterols. Furthermore, down-regulation of several hyphal and biofilm-related genes caused by heptanoic or nonanoic acid closely resembled the changes caused by farnesol. In addition, nonanoic acid, the most effective compound diminished C. albicans virulence in a Caenorhabditis elegans model. Our results suggest that medium-chain fatty acids inhibit more effectively hyphal growth and biofilm formation than farnesol.
| S-EPMC8313291 | biostudies-literature
Project description:Staphylococcus aureus, particularly drug-resistant strains, poses significant challenges in healthcare due to its ability to form biofilms, which confer increased resistance to antibiotics and immune responses. Building on previous knowledge that several flavonoids exhibit antibiofilm activity, this study sought to identify a novel flavonoid capable of effectively inhibiting biofilm formation and virulence factor production in S. aureus strains including MRSA. Among the 19 flavonoid-like compounds tested, 3,2'-dihydroxyflavone (3,2'-DHF) was identified for the first time as inhibiting biofilm formation and virulence factors in S. aureus with an MIC 75 µg/mL. The antibiofilm activity was further confirmed by microscopic methods. Notably, 3,2'-DHF at 5 µg/mL was effective in inhibiting both mono- and polymicrobial biofilms involving S. aureus and Candida albicans, a common co-pathogen. 3,2'-DHF reduces hemolytic activity, slime production, and the expression of key virulence factors such as hemolysin gene hla and nuclease gene nuc1 in S. aureus. These findings highlight the potential of 3,2'-DHF as a novel antibiofilm and antivirulence agent against both bacterial and fungal biofilms, offering a promising alternative to traditional antibiotics in the treatment of biofilm-associated infections.
| S-EPMC11311418 | biostudies-literature
Project description:Temporins are one of the largest families of antimicrobial peptides with both anti-inflammatory and antimicrobial activity. Herein, for a panel of cyclic temporin L isoform analogues, the antifungal and antibiofilm activities were determined against representative Candida strains, including C. albicans, C. glabrata, C. auris, C. parapsilosis and C. tropicalis. The outcomes indicated a significant anti-candida activity against planktonic and biofilm growth for four peptides (3, 7, 15 and 16). The absence of toxicity up to high concentrations and survival after infection were assessed in vivo by using Galleria mellonella larvae, and the correlation between conformation and cytotoxicity was investigated by fluorescence assays and circular dichroism (CD). By combining fluorescence spectroscopy, CD, dynamic light scattering, confocal and atomic force microscopy, the mode of action of four analogues was hypothesized. The results pinpointed that peptide 3 emerged as a non-toxic compound showing a potent antibiofilm activity and represents a promising compound for biomedical applications.
| S-EPMC8877061 | biostudies-literature
Project description:ImportanceThe persistence of Candida infections is due to its ability to form biofilms that enable it to resist antifungals and host immune systems. Hence, inhibitions of the biofilm formation and virulence characteristics of Candida sp. provide potential means of addressing these infections. Among various chromone derivatives tested, four chromone-3-carbonitriles showed antifungal, antibiofilm, and antivirulence activities against several Candida species. Their mode of action has been partially revealed, and their toxicity is reported here using nematode and plant models.
| S-EPMC10714962 | biostudies-literature
Project description:Substantial drug resistance afforded by Candida albicans biofilms results in ineffective treatment with conventional drugs and persistent infection. Our previous study showed that hexyl-aminolevulinate ethosomes (HAL-ES) act against C. albicans biofilms and weaken their drug resistance and pathogenicity; however, the mechanism involved remains unclear. Here, we systematically evaluated the effects and mechanisms of HAL-ES on biofilm formation and drug resistance. We found that, in addition to mediating antifungal photodynamic therapy, HAL-ES inhibited the early, developmental, and mature stages of biofilm formation compared with fluconazole, HAL, or ES. Notably, adhesion and hyphal formation were significantly inhibited by postdrug effects even after brief exposure (2 h) to HAL-ES. Its therapeutic effect in vivo also has been demonstrated in cutaneous candidiasis. RNA sequencing and quantitative PCR showed that HAL-ES inhibited ribosome biogenesis by disrupting zinc homeostasis in C. albicans, thereby reducing the translation process during protein synthesis. Furthermore, HAL-ES downregulated the expression of multidrug resistance genes and increased fluconazole susceptibility in C. albicans. Our findings provide a novel and efficient method for the treatment of biofilm resistance in C. albicans infection as well as a basis for the application of HAL-ES. We also describe a new strategy for the treatment of biofilm-related infections via zinc restriction. IMPORTANCE Candida albicans is the most prevalent fungal species of the human microbiota. The medical impact of C. albicans on its human host depends on its ability to form biofilms. The intrinsic resistance conferred by biofilms to conventional antifungal drugs makes biofilm-based infections a significant clinical challenge. In this study, we demonstrate the attenuating effect of HAL-ES on C. albicans biofilm formation and drug resistance. Furthermore, we propose that HAL-ES inhibits protein translation by disrupting zinc homeostasis in C. albicans. This study not only provides a novel and effective therapeutic strategy against C. albicans biofilm but also proposes a new strategy to resolve C. albicans biofilm infection by disrupting zinc homeostasis.
| S-EPMC9769717 | biostudies-literature
Project description:Candida species are a leading source of healthcare infections globally. The limited number of antifungal drugs combined with the isolation of Candida species, namely C. albicans and C. auris, exhibiting resistance to current antifungals necessitates the development of new therapeutics. The present study tested 85 synthetic phenylthiazole small molecules for antifungal activity against drug-resistant C. albicans. Compound 1 emerged as the most potent molecule, inhibiting growth of C. albicans and C. auris strains at concentrations ranging from 0.25-2 µg/mL. Additionally, compound 1 inhibited growth of other clinically-relevant yeast (Cryptococcus) and molds (Aspergillus) at a concentration as low as 0.50 µg/mL. Compound 1 exhibited rapid fungicidal activity, reducing the burden of C. albicans and C. auris below the limit of detection within 30 minutes. Compound 1 exhibited potent antibiofilm activity, similar to amphotericin B, reducing the metabolic activity of adherent C. albicans and C. auris biofilms by more than 66% and 50%, respectively. Furthermore, compound 1 prolonged survival of Caenorhabditis elegans infected with strains of C. albicans and C. auris, relative to the untreated control. The present study highlights phenylthiazole small molecules, such as compound 1, warrant further investigation as novel antifungal agents for drug-resistant Candida infections.
| S-EPMC6908612 | biostudies-literature
Project description:Candida albicans is a commensal coloniser of the human gastrointestinal tract and an opportunistic pathogen, especially thanks to its capacity to form biofilms. This lifestyle is frequently involved in infections and increases the yeast resistance to antimicrobials and immune defenses. In this context, 38 lichen acetone extracts have been prepared and evaluated for their activity against C. albicans planktonic and sessile cells. Minimum inhibitory concentrations of extracts (MICs) were determined using the broth microdilution method. Anti-biofilm activity was evaluated using tetrazolium salt (XTT) assay as the ability to inhibit the maturation phase (anti-maturation) or to eradicate a preformed 24 h old biofilm (anti-biofilm). While none of the extracts were active against planktonic cells, biofilm maturation was limited by 11 of the tested extracts. Seven extracts displayed both anti-maturation and anti-biofilm activities (half maximal inhibitory concentrations IC50_mat and IC50_biof ≤ 100 µg/mL); Evernia prunastri and Ramalina fastigiata were the most promising lichens (IC50_mat < 4 µg/mL and IC50_biof < 10 µg/mL). Chemical profiles of the active extracts performed by thin layer chromatography (TLC) and high performance liquid chromatography (HPLC) have been analyzed. Depsides, which were present in large amounts in the most active extracts, could be involved in anti-biofilm activities. This work confirmed that lichens represent a reservoir of compounds with anti-biofilm potential.
| S-EPMC6154547 | biostudies-literature