Antifungal activity of MAF-1A peptide against Candida albicans.
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ABSTRACT:
SUBMITTER: Cheng R
PROVIDER: S-EPMC8046747 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Candida albicans is a major fungal pathogen in humans. Novel antifungal agents are urgent demanded due to the challenges of the resistance. Antimicrobial peptides (AMPs) are critical components of the innate immune system against pathogenic microorganism infection. MAF-1A is a novel cationic AMP that comes from Musca domestica and is effective against C. albicans, but the antifungal mechanism remains unclear. In this study, we performed a transcriptomics analysis in C. albicans using RNA-seq technique under the treatment of MAF-1A. A total of 5654 genes were identified. Among these, 1032 were differentially expressed genes (DEGs), including 575 up-regulated genes and 457 down-regulated genes. In these DEGs, genes encoding ergosterol metabolism and fatty acid biosynthesis were identified to be significantly down-regulated, while genes associated with oxidative stress response and cell wall were identified to be significantly up-regulated. Using pathway enrichment analysis, 12 significant metabolic pathways were identified, and ribosome, oxidative phosphorylation, citrate cycle were mainly involved. The results revealed that MAF-1A induces complex responses in C. albicans. This study provides evidence that MAF-1A may inhibit the growth through affect multi-targets in C. albicans cells.
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Project description:Candida parapsilosis is a major fungal pathogen that leads to sepsis. New and more effective antifungal agents are required due to the emergence of resistant fungal strains. MAF-1A is a cationic antifungal peptide isolated from Musca domestica that is effective against a variety of Candida species. However, the mechanism(s) of its antifungal activity remains undefined. Here, we used RNA-seq to identify differentially expressed genes (DEGs) in Candida parapsilosis following MAF-1A exposure. The early (6 h) response included 1,122 upregulated and 1,065 downregulated genes. Late (18 h) responses were associated with the increased expression of 101 genes and the decreased expression of 151 genes. Upon MAF-1A treatment for 18 h, 42 genes were upregulated and 25 genes were downregulated. KEGG enrichment showed that the DEGs in response to MAF-1A were mainly involved in amino acid synthesis and metabolism, oxidative phosphorylation, sterol synthesis, and apoptosis. These results indicate that MAF-1A exerts antifungal activity through interference with Candida parapsilosis cell membrane integrity and organelle function. This provides new insight into the interaction between Candida parapsilosis and this antimicrobial peptide and serves as a reference for future Candida parapsilosis therapies.
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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.
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Project description:Human serum amyloid A (SAA) is a major acute phase protein and shows a massive increase of concentration in plasma during inflammation. In the current study, we report that recombinant human and mouse SAA1 (rhSAA1 and rmSAA1) have a potent antifungal activity against the major fungal pathogen Candida albicans. rhSAA1 binds to the cell surface of C. albicans and promotes cell aggregation. At high concentrations, rhSAA1 disrupts the membrane integrity and induces rapid cell death of C. albicans. Further investigation demonstrates that rhSAA1 targets on the cell wall adhesin Als3 of C. albicans. Inactivation of ALS3 in C. albicans leads to remarkably decreased cell aggregation and death upon rhSAA1 treatment, implying that Als3 plays a critical role in SAA1 sensing. Moreover, deletion of the ALS3 transcriptional regulators such as AHR1, BCR1, and EFG1 in C. albicans results in a similar effect on cell responses to that of the als3/als3 mutant upon rhSAA1 treatment. Global gene expression profiling analysis indicates that rhSAA1 has a remarkable impact on the expression of cell wall- and metabolism-related genes in C. albicans. Our finding of the antifungal activity of rhSAA1 against C. albicans expands the function of this protein and would provide new insights into the understanding of the host-Candida interaction during infections.
2019-09-01 | GSE128598 | GEO
Project description:Many studies have reported that hypocrellin A (HA) exhibits effective antimicrobial activities with proper irradiation. However, its antifungal activity and the involved mechanism have not been fully defined. In this study, HA-mediated cytotoxicity in Candida albicans cells was evaluated after antimicrobial photodynamic therapy (aPDT). The results showed that 1.0 μg/ml HA significantly decreased the survival rate of C. albicans cells with light illumination. Moreover, the ROS levels were also remarkably elevated by HA. Further study found that HA combined with illumination led to cell membrane potential depolarization and cell membrane integrity damage. To investigate the form of cell death, a series of apoptosis-related parameters, including mitochondrial transmembrane potential, metacaspase activity, DNA fragmentation, nuclear condensation, and cytosolic and mitochondrial calcium, were analyzed. Data showed that all the above mentioned apoptosis hallmarks were affected after treatment with HA, indicating that HA induced C. albicans cell apoptosis. Finally, HA-mediated aPDT was demonstrated to be low-toxic and effective in treating cutaneous C. albicans infections. This study highlights the antifungal effect and mechanism of HA-mediated aPDT against C. albicans and provides a promising photodynamic antifungal candidate for C. albicans skin infections.
| S-EPMC6691099 | biostudies-literature
Project description:Lactoferricin (Lfcin) is an amphipathic, cationic peptide derived from proteolytic cleavage of the N-lobe of lactoferrin (Lf). Lfcin and its derivatives possess broad-spectrum antibacterial and antifungal activities. However, unlike their antibacterial functions, the modes of action of Lfcin and its derivatives against pathogenic fungi are less well understood. In this study, the mechanisms of LfcinB15, a derivative of bovine Lfcin, against Candida albicans were, therefore, extensively investigated. LfcinB15 exhibited inhibitory activity against planktonic cells, biofilm cells, and clinical isolates of C. albicans and non-albicans Candida species. We further demonstrated that LfcinB15 is localized on the cell surface and vacuoles of C. albicans cells. Moreover, LfcinB15 uses several different methods to kill C. albicans, including disturbing the cell membrane, inducing reactive oxygen species (ROS) generation, and causing mitochondrial dysfunction. Finally, the Hog1 and Mkc1 mitogen-activated protein kinases were both activated in C. albicans cells in response to LfcinB15. These findings help us to obtain more insight into the complex mechanisms used by LfcinB15 and other Lfcin-derived peptides to fight fungal pathogens.
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Project description:Monolaurin (also known as glycerol monolaurate) is a natural compound found in coconut oil and is known for its protective biological activities as an antimicrobial agent. The nature of oral candidiasis and the increased antifungal resistance demand the search for novel antifungal therapeutic agents. In this study, we examine the antifungal activity of monolaurin against Candida albicans biofilms (strain ATCC:SC5314/MYA2876) in vitro and investigate whether monolaurin can alter gene expression of host inflammatory cytokines, IL-1? and IL-1?. In a co-culture model, oral fibroblast cells were cultured simultaneously with C. albicans for 24 hrs followed by the exposure to treatments of monolaurin (3.9-2,500 µM), positive control fluconazole (32.2 µM), and vehicle control group (1% ethanol), which was a model used to evaluate the cytotoxicity of monolaurin on fibroblasts as well as to analyze morphological characteristics of biofilms through fluorescence microscopy. In addition, the co-culture model was used for RNA extraction of oral fibroblasts to assess gene expression of host inflammatory cytokines, using quantitative real-time PCR. Our results showed the MIC and MFC of monolaurin were in the range 62.5-125 µM and 125-250 µM, respectively. Biofilm antifungal assay showed significant reduction in Log (CFU/ml) of biofilms treated with 1,250 and 2,500 µM of 1-monolaurin when compared to the control groups . There was also a significant down-regulation of IL-1? and IL-1? in the co-culture treated with monolaurin. It can be concluded that monolaurin has a potential antifungal activity against C. albicans and can modulate the pro-inflammatory response of the host.
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Project description:Mammalian serum amyloid A (SAA) is a major acute phase protein that shows a massive increase in plasma concentration during inflammation. In the present study, we demonstrate that the expression of mouse SAA1 in serum was increased when infected with Candida albicans, a major human fungal pathogen, in a systemic infection model. We then set out to investigate the antifungal activity of SAA proteins against C. albicans Recombinant human and mouse SAA1 (rhSAA1 and rmSAA1) were expressed and purified in Escherichia coli Both rhSAA1 and rmSAA1 exhibited a potent antifungal activity against C. albicans We further demonstrate that rhSAA1 binds to the cell surface of C. albicans, disrupts cell membrane integrity, and induces rapid fungal cell death in C. albicans Our finding expands the known functions of SAA1 and provides new insight into host-Candida interactions during fungal infection.
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Project description:We have previously reported on the activity of different extracts from Astronium sp. against Candida albicans, with the hydroethanolic extract prepared from leaves of A. urundeuva, an arboreal species widely distributed in arid environments of South America and often used in folk medicine, displaying the highest in vitro activity. Here we have further evaluated the antifungal activity of this extract against strains of C. albicans and C. glabrata, the two most common etiological agents of candidiasis. The extract was tested alone and loaded into a nanostructured lipid system (10% oil phase, 10% surfactant and 80% aqueous phase, 0.5% Poloxamer 407®). In vitro susceptibility assays demonstrated the antifungal activity of the free extract and the microemulsion against both Candida species, with increased activity against C. glabrata, including collection strains and clinical isolates displaying different levels of resistance against the most common clinically used antifungal drugs. Checkerboard results showed synergism when the free extract was combined with amphotericin B against C. albicans. Serial passage experiments confirmed development of resistance to fluconazole but not to the free extract upon prolonged exposure. Although preformed biofilms were intrinsically resistant to treatment with the extract, it was able to inhibit biofilm formation by C. albicans at concentrations comparable to those inhibiting planktonic growth. Cytotoxicity assays in different cell lines as well as an alternative model using Artemia salina L. confirmed a good safety profile of the both free and loaded extracts, and an in vivo assay demonstrated the efficacy of the free and loaded extracts when used topically in a rat model of vaginal candidiasis. Overall, these results reveal the promise of the A. urundeuva leaves extract to be further investigated and developed as an antifungal.
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Project description:Coumarin (1,2-benzopyrone), an aromatic oxygen-containing heterocyclic compound, has various biological functions. Previous studies have demonstrated that coumarin and its derivatives exhibit antifungal activity against Candida albicans. In this study, we investigated the exact mechanism by which coumarin works against this fungus using Annexin V-FITC/PI double staining, TUNEL assay, and DAPI staining, and found that it induced a series of apoptotic features, including phosphatidylserine (PS) externalization, DNA fragmentation, and nuclear condensation. Moreover, it also induced cytochrome c release from the mitochondria to the cytoplasm and metacaspase activation. Further study revealed that intracellular reactive oxygen species (ROS) levels were increased and mitochondrial functions, such as mitochondrial membrane potential and mitochondrial morphology, were altered after treatment with coumarin. Cytosolic and mitochondrial Ca2+ levels were also found to be elevated. However, pretreatment with ruthenium red (RR), a known mitochondrial Ca2+ channel inhibitor, attenuated coumarin-mediated DNA fragmentation and metacaspase activity, indicating that the coumarin-induced C. albicans apoptosis is associated with mitochondrial Ca2+ influx. Finally, coumarin was found to be low-toxic and effective in prolonging the survival of C. albicans-infected mice. This study highlights the antifungal activity and mechanism of coumarin against C. albicans and provides a potential treatment strategy for C. albicans infection.
| S-EPMC6328497 | biostudies-literature