scholarly journals Diorcinol D Exerts Fungicidal Action against Candida albicans through Cytoplasm Membrane Destruction and ROS Accumulation

PLoS ONE ◽  
2015 ◽  
Vol 10 (6) ◽  
pp. e0128693 ◽  
Author(s):  
Ying Li ◽  
Wenqiang Chang ◽  
Ming Zhang ◽  
Xiaobin Li ◽  
Yang Jiao ◽  
...  
2008 ◽  
Vol 52 (11) ◽  
pp. 4081-4088 ◽  
Author(s):  
María T. Andrés ◽  
Monica Viejo-Díaz ◽  
José F. Fierro

ABSTRACT Human lactoferrin (hLf) induced an apoptosis-like phenotype in Candida albicans cells, which includes phosphatidylserine externalization, nuclear chromatin condensation, DNA degradation, and increased reactive oxygen species (ROS) production. Intracellular ROS accumulation was seen to correlate with candidacidal activity in hLf-treated cells. Mitochondrial activity was involved as indicated by mitochondrial depolarization and increased hLf resistance of cells preincubated with sordarin or erythromycin, the latter of which inhibits protein synthesis in mitoribosomes. Interestingly, Cl−- and K+-channel blockers prevented the hLf antimicrobial activity, but only when cells were pretreated with the blocking agent (tetraethylammonium) prior to the hLf-induced K+-release period. These results indicate for the first time that K+-channel-mediated K+ efflux is required for the progression of apoptosis-like process in yeast, suggesting that this essential apoptotic event of higher eukaryotes has been evolutionary conserved among species ranging from yeasts to humans.


2020 ◽  
Vol 8 (5) ◽  
pp. 749
Author(s):  
Alejandra Argüelles ◽  
Ruth Sánchez-Fresneda ◽  
José P. Guirao-Abad ◽  
Cristóbal Belda ◽  
José Antonio Lozano ◽  
...  

The potential fungicidal action of the natural extracts, carnosic acid (obtained from rosemary) and propolis (from honeybees’ panels) against the highly prevalent yeast Candida albicans, used herein as an archetype of pathogenic fungi, was tested. The separate addition of carnosic acid and propolis on exponential cultures of the standard SC5314 C. albicans strain caused a moderate degree of cell death at relatively high concentrations. However, the combination of both extracts, especially in a 1:4 ratio, induced a potent synergistic pattern, leading to a drastic reduction in cell survival even at much lower concentrations. The result of a mathematical analysis by isobologram was consistent with synergistic action of the combined extracts rather than a merely additive effect. In turn, the capacity of SC5314 cells to form in vitro biofilms was also impaired by the simultaneous presence of both agents, supporting the potential application of carnosic acid and propolis mixtures in the prevention and treatment of clinical infections as an alternative to antibiotics and other antifungal agents endowed with reduced toxic side effects.


2019 ◽  
Vol 20 (4) ◽  
Author(s):  
Tongtong Ren ◽  
Hangqi Zhu ◽  
Lei Tian ◽  
Qilin Yu ◽  
Mingchun Li

ABSTRACT Candida albicans is a common pathogenic fungus with high mortality in immunocompromised patients. However, the mechanism by which C. albicans invades host epithelial cells and causes serious tissue damage remains to be further investigated. In this study, we established the C. albicans–293T renal epithelial cell interaction model to investigate the mechanism of epithelial infection by this pathogen. It was found that C. albicans infection causes severe cell death and reactive oxygen species (ROS) accumulation in epithelial cells. Further investigations revealed that C. albicans infection might up-regulate expression of nicotinamide adenine dinucleotide phosphate (NAPDH) oxidase (NOX), inhibit the activity of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), and suppress the p38–Nrf2–heme oxygenase-1 (HO-1) pathway which plays an important role in the elimination of intracellular ROS. Furthermore, epithelial cell death caused by the fungal infection could be strikingly alleviated by addition of the antioxidant agent glutathione, indicating the critical role of ROS accumulation in cell death caused by the fungus. This study revealed that disturbance of the redox homeostasis system and ROS accumulation in epithelial cells is involved in cell death caused by C. albicans infection, which sheds light on the application of antioxidants in the suppression of tissue damage caused by fungal infection.


Biochimie ◽  
2012 ◽  
Vol 94 (8) ◽  
pp. 1784-1793 ◽  
Author(s):  
Ji Hong Hwang ◽  
In-sok Hwang ◽  
Qing-He Liu ◽  
Eun-Rhan Woo ◽  
Dong Gun Lee

2013 ◽  
Vol 62 (8) ◽  
pp. 1175-1183 ◽  
Author(s):  
Yuxin Chen ◽  
Hong Zeng ◽  
Jun Tian ◽  
Xiaoquan Ban ◽  
Bingxin Ma ◽  
...  

This work studied the antifungal mechanism of dill seed essential oil (DSEO) against Candida albicans. Flow cytometric analysis and inhibition of ergosterol synthesis were performed to clarify the mechanism of action of DSEO on C. albicans. Upon treatment of cells with DSEO, propidium iodide penetrated C. albicans through a lesion in its plasma membrane. DSEO also significantly reduced the amount of ergosterol. These findings indicate that the plasma membrane of C. albicans was damaged by DSEO. The effect of DSEO on the functions of the mitochondria in C. albicans was also studied. We assayed the mitochondrial membrane potential (mtΔψ) using rhodamine 123 and determined the production of mitochondrial dysfunction-induced reactive oxygen species (ROS) via flow cytometry. The effects of the antioxidant l-cysteine (Cys) on DSEO-induced ROS production and the antifungal effect of DSEO on C. albicans were investigated. Exposure to DSEO increased mtΔψ. Dysfunctions in the mitochondria caused ROS accumulation in C. albicans. This increase in the level of ROS production and DSEO-induced decrease in cell viability were prevented by the addition of Cys, indicating that ROS are an important mediator of the antifungal action of DSEO. These findings indicate that the cytoplasmic membrane and mitochondria are the main anti-Candida targets of DSEO.


Author(s):  
Anatoly L. Kosakovsky ◽  
Oksana M. Golovnya ◽  
Svitlana G. Gunko ◽  
Ilona A. Kosakivska

Introduction: The causative agents of acute tonsillopharyngitis are viruses and bacterial flora. Treatment of acute pharyngitis is mainly local, which includes aerosols with antiseptics. Aim: Study of antimicrobial action of "Apicold oral spray" on clinical isolates of microorganisms Streptococcus pyogenes, Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Moraxella catarrhalis and Candida albicans isolated from patients' oropharynx in patients. Material and methods: The effect of Apicold Oral Spray (manufactured by APIPHARMA doo) on clinical isolates of Streptococcus pyogenes, Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Moraxella catarrhalis, and Candida albicans in Ukrainian patients was studied. Antimicrobial activity was assessed after 5, 10 and 20 minutes of action of one dose of "Apicold oral spray" on microorganisms. Bactericidal and fungicidal action (inhibition of cell growth of microorganisms) is expressed as a percentage according to the control. Results and discussion: Apicold Oral Spray has a 100% antimicrobial effect after 5 minutes on clinical isolates of Streptococcus pyogenes, Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Moraxella catarrhalis and Candida albicans (complete growth inhibition of all 5 clinical isolates after 20 minutes). Conclusion: "Apicold oral spray" has a high antimicrobial effect on clinical isolates of Streptococcus pyogenes, Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Moraxella catarrhalis and Candida albicans, which is confirmed by 100% inhibition of the growth of all bacteria after 5 minutes


2004 ◽  
Vol 48 (1) ◽  
pp. 110-115 ◽  
Author(s):  
David Wunder ◽  
Jin Dong ◽  
Didi Baev ◽  
Mira Edgerton

ABSTRACT Salivary histatins (Hsts) are potent candidacidal proteins that induce a nonlytic form of cell death in Candida albicans accompanied by loss of mean cell volume, cell cycle arrest, and elevation of intracellular levels of reactive oxygen species (ROS). Since these phenotypes are often markers of programmed cell death and apoptosis, we investigated whether other classical markers of apoptosis, including generation of intracellular ROS and protein carbonyl groups, chromosomal fragmentation (laddering), and cytochrome c release, are found in Hst 5-mediated cell death. Increased intracellular levels of ROS in C. albicans were detected in cells both following exogenous application of Hst 5 and following intracellular expression of Hst 5. However, Western blot analysis failed to detect specifically increased protein carbonylation in Hst 5-treated cells. There was no evidence of chromosomal laddering and no cytochrome c release was observed following treatment of C. albicans mitochondria with Hst 5. Superoxide dismutase enzymes of C. albicans and Saccharomyces cerevisiae provide essential protection against oxidative stress; therefore, we tested whether SOD mutants have increased susceptibility to Hst 5, as expected if ROS mediate fungicidal effects. Cell survival of S. cerevisiae SOD1/SOD2 mutants and C. albicans SOD1 mutants following Hst 5 treatment (31 μM) was indistinguishable from the survival of wild-type cells treated with Hst 5. We conclude that ROS may not play a direct role in fungicidal activity and that Hst 5 does not initiate apoptosis or programmed cell death pathways.


2020 ◽  
Vol 8 (4) ◽  
pp. 585 ◽  
Author(s):  
Ruei-Ching Chen ◽  
Chung-Yu Lan

Hepcidin 25 (hep 25) is a cysteine-rich 25-amino acid antimicrobial peptide containing the amino-terminal Cu(II)/Ni(II)-binding (ATCUN) motif. Upon metal binding, the ATCUN motif is known to be involved in the generation of reactive oxygen species (ROS), especially hydrogen peroxide and hydroxyl radicals, which act against different bacterial species. However, the antifungal activity and its correlation to the Cu(II)-ATCUN complex of Hep 25 are still poorly understood. Here, we found that ROS accumulation plays an important role in the fungicidal activity of hep 25 against Candida albicans. In addition, Annexin V-FITC staining and TUNEL assay results provide clues about the apoptosis induced by hep 25. Moreover, hep 25 also increases the generation of ROS, possibly because of copper binding to the ATCUN motif, which is relevant to its activity against C. albicans. Finally, the C. albicans killing action of hep 25 is an energy- and temperature-dependent process that does not involve targeting the membrane. Taken together, our results provide new insights into the mechanisms of hep 25 against C. albicans cells and the potential use of hep 25 and its derivatives as novel antifungal agents.


2017 ◽  
Vol 307 (4-5) ◽  
pp. 241-248 ◽  
Author(s):  
José P. Guirao-Abad ◽  
Ruth Sánchez-Fresneda ◽  
Begoña Alburquerque ◽  
José A. Hernández ◽  
Juan-Carlos Argüelles

2020 ◽  
Vol 8 (12) ◽  
pp. 1867
Author(s):  
Rebeca Alonso-Monge ◽  
José P. Guirao-Abad ◽  
Ruth Sánchez-Fresneda ◽  
Jesús Pla ◽  
Genoveva Yagüe ◽  
...  

In fungi, the Mitogen-Activated Protein kinase (MAPK) pathways sense a wide variety of environmental stimuli, leading to cell adaptation and survival. The HOG pathway plays an essential role in the pathobiology of Candida albicans, including the colonization of the gastrointestinal tract in a mouse model, virulence, and response to stress. Here, we examined the role of Hog1 in the C. albicans response to the clinically relevant antifungal Micafungin (MF), whose minimum inhibitory concentration (MIC) was identical in the parental strain (RM100) and in the isogenic homozygous mutant hog1 (0.016 mg/L). The cell viability was impaired without significant differences between the parental strain, the isogenic hog1 mutant, and the Hog1+ reintegrant. This phenotype was quite similar in a collection of hog1 mutants constructed in a different C. albicans background. MF-treated cells failed to induce a relevant increase of both reactive oxygen species (ROS) formation and activation of the mitochondrial membrane potential in parental and hog1 cells. MF was also unable to trigger any significant activation of the genes coding for the antioxidant activities catalase (CAT1) and superoxide dismutase (SOD2), as well as on the corresponding enzymatic activities, whereas a clear induction was observed in the presence of Amphotericin B (AMB), introduced as a positive control of Hog1 signaling. Furthermore, Hog1 was not phosphorylated by the addition of MF, but, notably, this echinocandin caused Mkc1 phosphorylation. Our results strongly suggest that the toxic effect of MF on C. albicans cells is not mediated by the Hog1 MAPK and is independent of the generation of an internal oxidative stress in C. albicans.


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