scholarly journals The Antibacterial Synthetic Flavonoid BrCl-Flav Exhibits Important Anti-Candida Activity by Damaging Cell Membrane Integrity

2021 ◽  
Vol 14 (11) ◽  
pp. 1130
Author(s):  
Cornelia Babii ◽  
Mihaela Savu ◽  
Iuliana Motrescu ◽  
Lucian Mihail Birsa ◽  
Laura Gabriela Sarbu ◽  
...  
Keyword(s):  
Antifungal Agents ◽  
Treatment Options ◽  
Membrane Integrity ◽  
Fungal Growth ◽  
Candida Spp ◽  
Antifungal Effect ◽  
Cell Membrane Integrity ◽  
Minimum Fungicidal Concentration ◽  
Good Potential ◽  
Time Kill

Infections caused by Candida are very difficult to treat due to increasing antifungal resistance. Recent studies showed that patients with Candida infections resistant to fluconazole have very few treatment options. Therefore, finding new efficient antifungal agents is a matter of medical high priority. The aim of this study was to explore the antifungal potential of BrCl-flav-a representative of a new class of synthetic flavonoids with bromine as halogen substituent at the benzopyran core against four Candida clinical strains. Determination of minimum inhibitory concentration and minimum fungicidal concentration along with the time kill assay indicated a strong antifungal effect of BrCl-flav against C. albicans, C. parapsilosis, C. krusei and C. glabrata. The investigation of anti-Candida mechanism of action using fluorescence microscopy and scanning electron microscopy revealed that Br-Cl flav could inhibit fungal growth by impairing the membrane integrity, the resulting structural damages leading to cell lysis. BrCl-flav also showed important anti-virulence properties against Candida spp., inhibiting biofilm formation and yeast to hyphal transition. A strong synergistic antifungal effect against C. albicans strain was observed when BrCl-flav was used in combination with fluconazole. BrCl-flav has a good potential to develop new effective antifungal agents in the context of Candida spp. multidrug resistance phenomenon.

scholarly journals Citronellal Exerts Its Antifungal Activity by Targeting Ergosterol Biosynthesis in Penicillium digitatum

2021 ◽  
Vol 7 (6) ◽  
pp. 432
Author(s):  
Qiuli OuYang ◽  
Yangmei Liu ◽  
Okwong Reymick Oketch ◽  
Miaoling Zhang ◽  
Xingfeng Shao ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Antifungal Agents ◽  
Inhibitory Concentration ◽  
Membrane Integrity ◽  
Penicillium Digitatum ◽  
Ergosterol Biosynthesis ◽  
Cell Membrane Integrity ◽  
Minimum Fungicidal Concentration ◽  
Green Mold ◽  
Erg Genes

Ergosterol (ERG) is a potential target for the development of antifungal agents against Penicillium digitatum, the pathogen of green mold in citrus fruits. This study examined the mechanism by which citronellal, a typical terpenoid of Cymbopogon nardus essential oil, acts on ergosterol to exhibit its antifungal activity against P. digitatum. We previously reported that citronellal inhibited the growth of P. digitatum with minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of 1.36 and 2.72 mg/mL, respectively. In citronellal-treated cells, the membrane integrity and ergosterol contents significantly decreased, whereas lanosterol, which serves as a precursor for ergosterol biosynthesis, massively accumulated. Addition of 150 mg/L of exogenous ergosterol decreased the inhibitory rate of citronellal, restoring the ergosterol content and hence the membrane structure to normal levels, and triggered expression of nearly all ERG genes. Based on our findings, we deduce that citronellal damages the cell membrane integrity of P. digitatum by down-regulating the ERG genes responsible for conversion of lanosterol to ergosterol, the key downregulated gene being ERG3, due to the observed accumulation of ergosta-7,22-dienol.

scholarly journals Biodirected Synthesis of Silver Nanoparticles Using Aqueous Honey Solutions and Evaluation of Their Antifungal Activity against Pathogenic Candida Spp.

2021 ◽  
Vol 22 (14) ◽  
pp. 7715
Author(s):  
Grzegorz Czernel ◽  
Dominika Bloch ◽  
Arkadiusz Matwijczuk ◽  
Jolanta Cieśla ◽  
Monika Kędzierska-Matysek ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Antifungal Activity ◽  
Fungal Pathogens ◽  
Fungal Growth ◽  
Disc Diffusion ◽  
Candida Spp ◽  
Antifungal Effect ◽  
Synthesis Of Nanoparticles ◽  
Honey Solution ◽  
Diffusion Assay

Silver nanoparticles (AgNPs) were synthesized using aqueous honey solutions with a concentration of 2%, 10%, and 20%—AgNPs-H2, AgNPs-H10, and AgNPs-H20. The reaction was conducted at 35 °C and 70 °C. Additionally, nanoparticles obtained with the citrate method (AgNPs-C), while amphotericin B (AmB) and fluconazole were used as controls. The presence and physicochemical properties of AgNPs was affirmed by analyzing the sample with ultraviolet–visible (UV–Vis) and fluorescence spectroscopy, scanning electron microscopy (SEM), and dynamic light scattering (DLS). The 20% honey solution caused an inhibition of the synthesis of nanoparticles at 35 °C. The antifungal activity of the AgNPs was evaluated using opportunistic human fungal pathogens Candida albicans and Candida parapsilosis. The antifungal effect was determined by the minimum inhibitory concentration (MIC) and disc diffusion assay. The highest activity in the MIC tests was observed in the AgNPs-H2 variant. AgNPs-H10 and AgNPs-H20 showed no activity or even stimulated fungal growth. The results of the Kirby–Bauer disc diffusion susceptibility test for C. parapsilosis strains indicated stronger antifungal activity of AgNPs-H than fluconazole. The study demonstrated that the antifungal activity of AgNPs is closely related to the concentration of honey used for the synthesis thereof.

scholarly journals Whether Supercritical Extracts from the Aerial Parts of Helianthus salicifolius and Helianthus tuberosus May be Regarded as a Potential Raw Materials for Non-bioenergy Purposes?

2020 ◽  
Author(s):  
Anna Malm ◽  
Agnieszka Grzegorczyk ◽  
Anna Biernasiuk ◽  
Tomasz Baj ◽  
Edward Rój ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Raw Materials ◽  
Bactericidal Effect ◽  
Helianthus Tuberosus ◽  
Candida Spp ◽  
Minimum Fungicidal Concentration ◽  
Aerial Parts ◽  
Antistaphylococcal Activity ◽  
Time Kill

The extracts from the aerial parts of Helianthus salicifolius A. Dietr and Helianthus tuberosus L. collected in June were obtained using carbon dioxide supercritical fluid extraction with water as co-solvent. The antimicrobial activity in vitro of these extracts were determined against the reference species of Gram-positive and Gram-negative bacteria as well as fungi, representing by the yeast species of Candida spp. The following parameters were estimated: minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) or minimum fungicidal concentration (MFC). Both extracts were found to possess antimicrobial activity with MIC = 0.62-5 mg mL-1 for bacteria and MIC = 5-10 mg mL-1 for yeasts, showing bactericidal (MBC/MIC = 2-4) or fungicidal effect (MFC/MIC = 1-2 ). The highest activity was observed against S. aureus ATCC 29213 (MIC = 0.62 mg mL-1 for H. salicifolius extract; MIC = 2.5 mg mL-1 for H. tuberosus extract). Bactericidal effect of both extracts against S. aureus ATCC 29213 was confirmed by time-kill assay. Higher antioxidant activity was found for H. tuberosus extract (EC50 = 0.332 mg mL-1) as compared to that of H. salicifolius (EC50 = 0.609 mg mL-1). The total polyphenol content (TPC) expressed as gallic acid equivalents (GAE) was 13.75 ± 0.50 mg GAE (g of H. salicifolius extract)-1 and 33.06 ± 0.80 mg GAE (g of H. tuberosus extract)-1. There was a correlation between the antioxidant potential of both extracts and TPC but not between antistaphylococcal activity and TPC. The obtained data suggest potential application of these extracts as the natural preparations with the biocidal activity, including those with antistaphylococcal activity. Besides, both extracts may be regarded as potential natural conservants in cosmetics as well as natural preservatives in food.

scholarly journals Inhibitory Effect of (-)-myrtenol alone and in combination with antifungal agents on Candida spp.

2021 ◽  
Vol 10 (15) ◽  
pp. e35101522434
Author(s):  
Bruno Bezerra Cavalcanti ◽  
Hermes Diniz Neto ◽  
Walicyranison Plinio da Silva-Rocha ◽  
Edeltrudes de Oliveira Lima ◽  
José Maria Barbosa Filho ◽  
...  
Keyword(s):  
Minimum Inhibitory Concentration ◽  
Antifungal Agent ◽  
Antifungal Agents ◽  
Inhibitory Concentration ◽  
Inhibitory Effect ◽  
Antifungal Drugs ◽  
Additive Effects ◽  
Candida Spp ◽  
Minimum Fungicidal Concentration ◽  
Fungicide Activity

The aim of this study was to examine the effects of (-)-myrtenol alone and combined with antifungal agents against Candida spp. The Minimum Inhibitory Concentration (MIC) and Minimum Fungicidal Concentration of (-)-myrtenol and fluconazole against C. albicans and C. parapsilosis strains was obtained using CLSI guidelines. Combination of (-)-myrtenol with antifungal drugs was determined by checkboard test. The (-) myrtenol showed MIC ranging from 256 to 512 µg/mL against both species assay. And the MFC was 512 µg/mL, demonstrated nature fungicidal (MFC/MIC < 4). In addition, combination of antifungal agents (amphotericin B and fluconazole) and (-) myrtenol showed synergistic and additive effects on strains assays. Based on these results, the present study demonstrates that (-) myrtenol showed strong fungicide activity against Candida spp. In addition, Combination of antifungal agents and (-) myrtenol reduces the effective concentrations of both the agents with synergistic to additive effects. Therefore, (-) myrtenol has potential to be developed into an antifungal agent.

Synergistic effects of ketamine and azole derivatives on Candida spp. resistance to fluconazole

2020 ◽  
Vol 15 (3) ◽  
pp. 177-188 ◽  
Author(s):  
João Batista de Andrade Neto ◽  
Cecília Rocha da Silva ◽  
Fátima Daiana Barroso ◽  
Lívia Gurgel do Amaral Valente Sá ◽  
Rosana de Sousa Campos ◽  
...  
Keyword(s):  
Concentration Index ◽  
Antifungal Agents ◽  
Inhibitory Concentration ◽  
Synergistic Effects ◽  
Membrane Integrity ◽  
Oxygen Species ◽  
Planktonic Cells ◽  
Candida Spp ◽  
Fractional Inhibitory Concentration Index ◽  
Drug Synergy

The emergence of Candida spp. with resistance to antifungal molecules, mainly the azole class, is an increasing complication in hospitals around the globe. Aim: In the present research, we evaluated the synergistic effects of ketamine with two azole derivatives, itraconazole and fluconazole, on strains of Candida spp. to fluconazole. Materials & methods: The drug synergy was evaluated by quantifying the fractional inhibitory concentration index and by fluorescence microscopy and flow cytometry techniques. Results: Our achievements showed a synergistic effect between ketamine in addition to the two antifungal agents (fluconazole and itraconazole) against planktonic cells and biofilms of Candida spp. Conclusion: This combination promoted alteration of membrane integrity, generation of reactive oxygen species, damage to and DNA and externalization of phosphatidylserine.

A Time-Kill Evaluation of Fluconazole and Amphotericin B against Candida Isolates

2000 ◽  
Vol 16 (3) ◽  
pp. 102-106 ◽  
Author(s):  
David S Burgess ◽  
Rhonda W Hastings ◽  
James S Lewis
Keyword(s):  
Amphotericin B ◽  
Fungal Growth ◽  
Resistant Isolate ◽  
Test Time ◽  
Candida Spp ◽  
Use Of Time ◽  
Dosing Regimens ◽  
Time Kill ◽  
Growth Controls ◽  
Dose Dependent

Objective: To compare the activity of fluconazole and amphotericin B against four isolates of Candida spp. with varying susceptibilities by use of time-kill methodology. Methods: Two isolates of Candida albicans and one isolate each of Candida tropicalis and Candida glabrata were used for all experiments. Susceptibilities were determined in duplicate by E-test. Time-kill studies were performed with fluconazole 1, 10, and 20 μg/mL and amphotericin B 0.25, 1, and 2.5 μg/mL. Samples were withdrawn at 0, 2, 8, 12, and 24 hours for fluconazole and at 0, 0.5, 1, 2, 4, 12, and 24 hours for amphotericin B, diluted if necessary, then plated on potato dextrose agar plates. After incubating plates at 35 °C for 24 hours, colony counts were determined. Results: The minimum inhibitory concentration of fluconazole and amphotericin B, respectively, were as follows: 0.75 and 0.25 μg/mL for C. albicans ATCC 90028, >256 and 0.25 μg/mL for C. albicans 1378, 2 and 1 μg/mL for C. tropicalis, and 12 and 0.125 μg/mL for C. glabrata. Differences observed in the activity of fluconazole were dependent on the Candida spp. and susceptibility to the drug. All three concentrations of fluconazole were fungistatic against C. albicans ATCC 90028 and ineffective against C. albicans 1378 (the resistant isolate). Fluconazole suppressed the growth of C. tropicalis for the initial eight hours, after which fungal growth resumed. Against C. glabrata, fluconazole was ineffective at 1 μg/mL, whereas the 10- and 20-μg/mL concentrations were fungistatic for the first 12 hours. Amphotericin B displayed a concentration-dependent effect against all four isolates of Candida spp. Conclusions: Fluconazole 10 and 20 μg/mL were either fungistatic or suppressive for each of the susceptible and susceptible dose-dependent Candida isolates for the initial eight to 12 hours. In addition, despite resumed fungal growth, final colony counts with these concentrations were decreased by >80% compared with the growth controls at 24 hours. By comparison, the activity of amphotericin B was dependent on concentration against all four isolates, and fungicidal activity was demonstrated with only the concentration of 2.5 μg/mL. These concentrations of fluconazole and amphotericin B are readily available with common, clinically used dosing regimens (i.e., fluconazole 400 mg qd and amphotericin B 1 mg/kg/d).

scholarly journals Colombian Essential Oil of Ruta graveolens against Nosocomial Antifungal Resistant Candida Strains

2021 ◽  
Vol 7 (5) ◽  
pp. 383
Author(s):  
Matthew Gavino Donadu ◽  
Yeimmy Peralta-Ruiz ◽  
Donatella Usai ◽  
Francesca Maggio ◽  
Junior Bernando Molina-Hernandez ◽  
...  
Keyword(s):  
Essential Oil ◽  
Antifungal Agents ◽  
Inhibitory Concentration ◽  
Membrane Integrity ◽  
Cellular Membrane ◽  
Ruta Graveolens ◽  
The Past ◽  
Immunosuppressed Patients ◽  
Time Kill ◽  
Fungistatic Effect

Drug resistance in antifungal therapy, a problem unknown until a few years ago, is increasingly assuming importance especially in immunosuppressed patients and patients receiving chemotherapy and radiotherapy. In the past years, the use of essential oils as an approach to improve the effectiveness of antifungal agents and to reduce antifungal resistance levels has been proposed. Our research aimed to evaluate the antifungal activity of Colombian rue, Ruta graveolens, essential oil (REO) against clinical strains of Candida albicans, Candida parapsilopsis, Candida glabrata, and Candida tropicalis. Data obtained showed that C. tropicalis and C. albicans were the most sensitive strains showing minimum inhibitory concentrations (MIC) of 4.1 and 8.2 µg/mL of REO. Time–kill kinetics assay demonstrated that REO showed a fungicidal effect against C. tropicalis and a fungistatic effect against C. albicans. In addition, an amount of 40% of the biofilm formed by C. albicans was eradicated using 8.2 µg/mL of REO after 1 h of exposure. The synergistic effect of REO together with some antifungal compounds was also investigated. Fractional inhibitory concentration index (FICI) showed synergic effects of REO combined with amphotericin B. REO Lead a disruption in the cellular membrane integrity, consequently resulting in increased intracellular leakage of the macromolecules, thus confirming that the plasma membrane is a target of the mode of action of REO against C. albicans and C. tropicalis.

scholarly journals In Vitro Activity of Micafungin (FK-463) against Candida spp.: Microdilution, Time-Kill, and Postantifungal-Effect Studies

2002 ◽  
Vol 46 (12) ◽  
pp. 3846-3853 ◽  
Author(s):  
Erika J. Ernst ◽  
Ellen E. Roling ◽  
C. Rosemarie Petzold ◽  
Douglas J. Keele ◽  
Michael E. Klepser
Keyword(s):  
Fungicidal Activity ◽  
Candida Krusei ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Candida Spp ◽  
Minimum Fungicidal Concentration ◽  
Inhibition Of Growth ◽  
Time Kill ◽  
Postantifungal Effect

ABSTRACT We evaluated the in vitro activity of the new echinocandin antifungal micafungin against Candida spp. using microdilution and time-kill methods. Additionally, we examined the postantifungal effect (PAFE) of micafungin. Finally, we evaluated the effect of the addition of serum and plasma on the MIC of micafungin. Four Candida albicans isolates and two isolates of each Candida glabrata, Candida krusei, and Candida tropicalis were selected for testing. The MICs of micafungin were determined in RPMI 1640 medium buffered with morpholinepropanesulfonic acid alone and with the addition of 10, 20, and 50% human serum and plasma. MICs were determined by using two endpoints: a prominent reduction in growth (the MIC at which 80% of isolates are inhibited [MIC80]) and complete visual inhibition of growth (MIC100). The minimum fungicidal concentration (MFC) of micafungin for each isolate was also determined. Time-kill curves were determined for each isolate in RPMI 1640 medium with micafungin at concentrations ranging from 0.125 to 16 times the MIC80 to assess the correlation between MIC80 and fungicidal activity. PAFE studies were conducted with each isolate by using concentrations ranging between 0.25 and 4 times the MIC80. The MIC80s for the test isolates ranged from 0.0039 to 0.25 μg/ml. Overall, the addition of serum or plasma increased the MIC 6 to 7 doubling dilutions for C. albicans and 3 to 4 doubling dilutions for C. krusei and C. tropicalis. Micafungin time-kill studies demonstrated fungicidal activity at concentrations ranging from 4 to 16 times the MIC80. Micafungin is very potent agent against a variety of Candida spp., producing fungicidal activity against 7 of 10 isolates tested. A PAFE was observed against all isolates. The PAFE was influenced by the drug concentration, with the highest concentration resulting in the longest observed PAFE in each case. The highest concentration tested, four times the MIC, resulted in a PAFE of more than 9.8 h for 5 of 10 isolates tested (range, 0.9 to ≥20.1 h).

Quercetin in attenuation of ischemic/reperfusion injury: A review

2020 ◽  
Vol 13 ◽  
Author(s):  
Milad Ashrafizadeh ◽  
Saeed Samarghandian ◽  
Kiavash Hushmandi ◽  
Amirhossein Zabolian ◽  
Md Shahinozzaman ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Membrane ◽  
Blood Supply ◽  
Apoptotic Cell ◽  
Ischemia Reperfusion ◽  
Membrane Integrity ◽  
Therapeutic Effects ◽  
Molecular Pathways ◽  
Cell Membrane Integrity ◽  
Cell Membrane Disruption

Background: Ischemia/reperfusion (I/R) injury is a serious pathologic event that occurs due to restriction in blood supply to an organ, followed by hypoxia. This condition leads to enhanced levels of pro-inflammatory cytokines such as IL-6 and TNF-, and stimulation of oxidative stress via enhancing reactive oxygen species (ROS) levels. Upon reperfusion, blood supply increases, but it deteriorates condition, and leads to generation of ROS, cell membrane disruption and finally, cell death. Plant derived-natural compounds are well-known due to their excellent antioxidant and anti-inflammatory activities. Quercetin is a flavonoid exclusively found in different vegetables, herbs, and fruits. This naturally occurring compound possesses different pharmacological activities making it appropriate option in disease therapy. Quercetin can also demonstrate therapeutic effects via affecting molecular pathways such as NF-B, PI3K/Akt and so on. Methods: In the present review, we demonstrate that quercetin administration is beneficial in ameliorating I/R injury via reducing ROS levels, inhibition of inflammation, and affecting molecular pathways such as TLR4/NF-B, MAPK and so on. Results and conclusion: Quercetin can improve cell membrane integrity via decreasing lipid peroxidation. Apoptotic cell death is inhibited by quercetin via down-regulation of Bax, and caspases, and upregulation of Bcl-2. Quercetin is able to modulate autophagy (inhibition/induction) in decreasing I/R injury. Nanoparticles have been applied for delivery of quercetin, enhancing its bioavailability and efficacy in alleviation of I/R injury. Noteworthy, clinical trials have also confirmed the capability of quercetin in reducing I/R injury.

Sign in / Sign up

Export Citation Format

Share Document