scholarly journals Tetrahedral DNA nanostructure improves transport efficiency and anti‐fungal effect of histatin 5 against Candida albicans

2021 ◽  
Author(s):  
Bowen Zhang ◽  
Xin Qin ◽  
Mi Zhou ◽  
Taoran Tian ◽  
Yue Sun ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Histatin 5 ◽  
Transport Efficiency ◽  
Dna Nanostructure ◽  
Anti Fungal

Effects of histatin 5 and derived peptides on Candida albicans

2001 ◽  
Vol 356 (2) ◽  
pp. 361-368 ◽  
Author(s):  
Anita L. A. RUISSEN ◽  
Jasper GROENINK ◽  
Eva J. HELMERHORST ◽  
Els WALGREEN-WETERINGS ◽  
Wim van't HOF ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Mitochondrial Membrane ◽  
Cytoplasmic Membrane ◽  
Human Saliva ◽  
Mitochondrial Activity ◽  
Complete Protection ◽  
Destructive Effect ◽  
Histatin 5 ◽  
Killing Activity ◽  
Anti Fungal

Three anti-microbial peptides were compared with respect to their killing activity against Candida albicans and their ability to disturb its cellular and internal membranes. Histatin 5 is an anti-fungal peptide occurring naturally in human saliva, while dhvar4 and dhvar5 are variants of its active domain, with increased anti-microbial activity. dhvar4has increased amphipathicity compared with histatin 5, whereas dhvar5has amphipathicity comparable with that of histatin 5. All three peptides caused depolarization of the cytoplasmic and/or mitochondrial membrane, indicating membranolytic activity. For the variant peptides both depolarization and killing occurred at a faster rate. With FITC-labelled peptides, no association with the cytoplasmic membrane was observed, contradicting the formation of permanent transmembrane multimeric peptide pores. Instead, the peptides were internalized and act on internal membranes, as demonstrated with mitochondrion- and vacuole-specific markers. In comparison with histatin 5, the variant peptides showed a more destructive effect on mitochondria. Entry of the peptides and subsequent killing were dependent on the metabolic state of the cells. Blocking of the mitochondrial activity led to complete protection against histatin 5 activity, whereas that of dhvar4 was hardly affected and that of dhvar5 was affected only intermediately.

scholarly journals Anti-Fungal Activity of Cathelicidins and their Potential Role in Candida albicans Skin Infection

2005 ◽  
Vol 125 (1) ◽  
pp. 108-115 ◽  
Author(s):  
Belén López-García ◽  
Phillip H.A. Lee ◽  
Kenshi Yamasaki ◽  
Richard L. Gallo
Keyword(s):  
Candida Albicans ◽  
Potential Role ◽  
Skin Infection ◽  
Fungal Activity ◽  
Anti Fungal

scholarly journals Interactions between Terpinen-4-ol and Nystatin on biofilm of Candida albicans and Candida tropicalis

2018 ◽  
Vol 29 (4) ◽  
pp. 359-367 ◽  
Author(s):  
Caroline Coradi Tonon ◽  
Renata Serignoli Francisconi ◽  
Ester Alves Ferreira Bordini ◽  
Patrícia Milagros Maquera Huacho ◽  
Janaína de Cássia Orlandi Sardi ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Enzymatic Activity ◽  
Candida Tropicalis ◽  
Microtiter Plate ◽  
Synergistic Activity ◽  
Oral Keratinocytes ◽  
Mixed Species ◽  
Colony Forming Units ◽  
Anti Fungal ◽  
Oral Cells

Abstract The aim of this study was to evaluate the antifungal activity of Terpinen-4-ol associated with nystatin, on single and mixed species biofilms formed by Candida albicans and Candida tropicalis, as well as the effect of terpinen-4-ol on adhesion in oral cells and the enzymatic activity. The minimum inhibitory concentrations and minimum fungicide concentrations of terpinen-4-ol and nystatin on Candida albicans and Candida tropicalis were determined using the microdilution broth method, along with their synergistic activity (“checkerboard” method). Single and mixed species biofilms were prepared using the static microtiter plate model and quantified by colony forming units (CFU/mL). The effect of Terpinen-4-ol in adhesion of Candida albicans and Candida tropicalis in coculture with oral keratinocytes (NOK Si) was evaluated, as well as the enzymatic activity by measuring the size of the precipitation zone, after the growth agar to phospholipase, protease and hemolysin. Terpinen-4-ol (4.53 mg mL-1) and nystatin (0.008 mg mL-1) were able to inhibit biofilms growth, and a synergistic antifungal effect was showed with the drug association, reducing the inhibitory concentration of nystatin up to 8 times in single biofilm of Candida albicans, and 2 times in mixed species biofilm. A small decrease in the adhesion of Candida tropicalis in NOK Si cells was showed after treatment with terpinen-4-ol, and nystatin had a greater effect for both species. For enzymatic activity, the drugs showed no action. The effect potentiated by the combination of terpinen-4-ol and nystatin and the reduction of adhesion provide evidence of its potential as an anti-fungal agent.

scholarly journals Candida albicans exhibits distinct cytoprotective responses to anti-fungal drugs that facilitate the evolution of drug resistance

2020 ◽  
Author(s):  
V Bettauer ◽  
S Massahi ◽  
S Khurdia ◽  
ACBP Costa ◽  
RP Omran ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Candida Albicans ◽  
Drug Exposure ◽  
Fluorescent Imaging ◽  
Late Time ◽  
Transport Mechanisms ◽  
Short Term ◽  
Anti Fungal ◽  
Initial Drug

AbstractWe developed a modified protocol for nanolitre droplet-based single cell sequencing appropriate for fungal settings, and used it to transcriptionally profiled several thousands cells from a prototrophic Candida albicans population and several drug exposed colonies (incl. fluconazole, caspofungin and nystatin). Thousands of cells from each colony were profiled both at early and late time points post-treatment in order to infer survival trajectories from initial drug tolerance to drug resistance. We find that prototrophic C. albicans populations differentially and stochastically express cytoprotective epigenetic programs. For all drugs, there is evidence that tolerant individuals partition into distinct subpopulations, each with a unique survival strategy involving different regulatory programs. These responses are weakly related to changes in morphology (shift from white to opaque forms, or shift from yeast to filamentous forms). In turn, those subpopulations that successfully reach resistance each have a distinct multivariate epigenetic response that coordinates the expression of efflux pumps, chaperones, transport mechanisms, and cell wall maintenance. Live cell fluorescent imaging was used to validate predictions of which molecular responses most often led to survival after drug exposure. Together our findings provide evidence that C. albicans has a robust toolkit of short-term epigenetic cytoprotective responses designed to “buy time” and increase the chance of acquiring long-term resistance.

Comprehensive GC-MS and FT-IR Profiling of Coleus zeylanicus essential oil and investigation of its anti-fungal and anti - oxidant activities

2021 ◽  
Vol 12 (1) ◽  
pp. 636-642
Author(s):  
Lakshmi M ◽  
Nandagopal S
Keyword(s):  
Antioxidant Activity ◽  
Candida Albicans ◽  
Essential Oil ◽  
Malassezia Furfur ◽  
Fungal Strains ◽  
Anti Oxidant ◽  
Ft Ir ◽  
Dpph Scavenging ◽  
Dpph Scavenging Assay ◽  
Anti Fungal

To evaluate the leaf volatile constituents of essential oil of Coleus zeylanicus and evaluate their anti-oxidant and anti-fungal activity. The Chemical composition of Coleus zeylanicus essential oil was determined using GC-MS and FT-IR analytical techniques. The antioxidant activity was evaluated using DPPH scavenging assay. The anti-fungal effect was tested against two potential pathogenic fungal strains - Candida albicans and Malassezia furfur using agar well diffusion method. The essential oil was profiled by the presence of sesquiterpene hydrocarbons 90.67% of their total composition followed by oxygenated monoterpenes and monoterpene hydrocarbons as 5.3% and 2.1% respectively. The GC-MS results showed 14 compounds from Coleus zeylanicus leaf EO representing 98.07% of the total oil composition. The major component was identified as a-Gurjunene (35.94%), a-bisabolol (10.82%) and G-selinene (4.26%). EO showed remarkable antioxidant activity values of IC50 = 59.78± 3.21µg/ml by DPPH scavenging assay. The essential oil showed interesting anti-fungal effects against two pathogenic fungal strains. The most sensible strains to Coleus zeylanicus EO was Malassezia furfur (32.00±0.50mm) compared to that of Candida albicans (15.00±1.25mm). Hence, Coleus zeylanicus EO has potential application against fungal infection and oxidative stress-related diseases. However, further investigations are necessary to isolate and investigate the action mechanism of these bioactive compounds.

scholarly journals Candida albicans Cek1 Mitogen-Activated Protein Kinase Signaling Enhances Fungicidal Activity of Salivary Histatin 5

2015 ◽  
Vol 59 (6) ◽  
pp. 3460-3468 ◽  
Author(s):  
Rui Li ◽  
Sumant Puri ◽  
Swetha Tati ◽  
Paul J. Cullen ◽  
Mira Edgerton
Keyword(s):  
Candida Albicans ◽  
Protein Kinase ◽  
Antifungal Drugs ◽  
Mitogen Activated Protein Kinase ◽  
Fungal Cell ◽  
Content Type ◽  
Histatin 5 ◽  
Mitogen Activated Protein ◽  
Hyphal Formation ◽  
Sensor Proteins

ABSTRACTCandida albicansis a major etiological organism for oropharyngeal candidiasis (OPC), while salivary histatin 5 (Hst 5) is a human fungicidal protein that protects the oral cavity from OPC.C. albicanssenses its environment by mitogen-activated protein kinase (MAPK) activation that can also modulate the activity of some antifungal drugs, including Hst 5. We found that phosphorylation of the MAPK Cek1, induced either byN-acetylglucosamine (GlcNAc) or serum, or its constitutive activation by deletion of its phosphatase Cpp1 elevated the susceptibility ofC. albicanscells to Hst 5. Cek1 phosphorylation but not hyphal formation was needed for increased Hst 5 sensitivity. Interference with the Cek1 pathway by deletion of its head sensor proteins, Msb2 and Sho1, or by addition of secreted aspartyl protease (SAP) cleavage inhibitors, such as pepstatin A, reduced Hst 5 susceptibility under Cek1-inducing conditions. Changes in fungal cell surface glycostructures also modulated Hst 5 sensitivity, and Cek1-inducing conditions resulted in a higher uptake rate of Hst 5. These results show that there is a consistent relationship between activation of Cek1 MAPK and increased Hst 5 susceptibility inC. albicans.

Internalisation and Degradation of Histatin 5 by Candida albicans

2003 ◽  
Vol 384 (1) ◽  
Author(s):  
A.L.A. Ruissen ◽  
J. Groenink ◽  
P. Krijtenberg ◽  
E. Walgreen-Weterings ◽  
W. van 't Hof ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Histatin 5

Phytosphingosine kills Candida albicans by disrupting its cell membrane

2010 ◽  
Vol 391 (1) ◽  
Author(s):  
Enno C.I. Veerman ◽  
Marianne Valentijn-Benz ◽  
Wim van't Hof ◽  
Kamran Nazmi ◽  
Jan van Marle ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Plasma Membrane ◽  
Adenine Nucleotides ◽  
Freeze Fracture ◽  
Direct Interaction ◽  
Histatin 5 ◽  
Membrane Probe ◽  
Ultrastructural Damage ◽  
Freeze Fracture Electron Microscopy ◽  
Fracture Electron

Abstract The mechanism of action of phytosphingosine (PHS), a member of the sphingosine family which has candidacidal activity when added externally, was investigated. Previously, it has been reported that the fungicidal activity of PHS is based on the induction of caspase-independent apoptosis. In contrast, we found that addition of PHS causes a direct permeabilization of the plasma membrane of yeast, highlighted by the influx of the membrane probe propidium iodide, and the efflux of small molecules (i.e., adenine nucleotides) as well as large cellular constituents such as proteins. Freeze-fracture electron microscopy revealed that PHS treatment causes severe damage of the plasma membrane of the cell, which seems to have lost its integrity completely. We also found that PHS reverts the azide-induced insensitivity to histatin 5 (Hst5) of Candida albicans. In a previous study, we had found that the decreased sensitivity to Hst5 of energy-depleted cells is due to rigidification of the plasma membrane, which could be reverted by the membrane fluidizer benzyl alcohol. In line with the increased membrane permeabilization and ultrastructural damage, this reversal of the azide-induced insensitivity by PHS also points to a direct interaction between PHS and the cytoplasmic membrane of C. albicans.

scholarly journals The P-113 Fragment of Histatin 5 Requires a Specific Peptide Sequence for Intracellular Translocation in Candida albicans, Which Is Independent of Cell Wall Binding

2007 ◽  
Vol 52 (2) ◽  
pp. 497-504 ◽  
Author(s):  
Woong Sik Jang ◽  
Xuewei Serene Li ◽  
Jianing N. Sun ◽  
Mira Edgerton
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Specific Binding ◽  
Peptide Sequence ◽  
Histatin 5 ◽  
Intracellular Targeting ◽  
Cell Wall Binding ◽  
Nacl Concentration ◽  
Lysine Residues ◽  
Intracellular Translocation

ABSTRACT The activity of histatin 5 (Hst 5) against Candida albicans is initiated through cell wall binding, followed by translocation and intracellular targeting. The C. albicans cell wall protein Ssa2 is involved in the transport of Hst 5 into cells as part of cell killing. P-113 (a 12-amino-acid candidacidal active fragment of Hst 5) and P-113Q2.10 (which is inactivated by a glutamine substitution of the Lys residues at positions 2 and 10) were compared for their levels of cell wall binding and intracellular translocation in Candida wild-type (wt) and ssa2Δ strains. Both P-113 and P-113Q2.10 bound to the walls of C. albicans wt and ssa2Δ cells, although the quantity of P-113Q2.10 in cell wall extracts was higher than that of P-113 in both strains. Increasing the extracellular NaCl concentration to 100 mM completely inhibited the cell wall association of both peptides, suggesting that these interactions are primarily ionic. The accumulation of P-113 in the cytosol of wt cells reached maximal levels within 15 min (0.26 μg/107 cells), while ssa2Δ mutant cells had maximal cytosolic levels of less than 0.2 μg/107 cells even after 30 min of incubation. Furthermore, P-113 but not P-113Q2.10 showed specific binding with a peptide array of C. albicans Ssa2p. P-113Q2.10 was not transported into the cytosol of either C. albicans wt or ssa2Δ cells, despite the high levels of cell wall binding, showing that the two cationic lysine residues at positions 2 and 10 in the P-113 peptide are important for transport into the cytosol and that binding and transport are independent functional events.

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