scholarly journals Control ofCryptococcus GattiiBiofilms by an Ethanolic Extract ofCochlospermum Regium(Schrank) Pilger Leaves

2018 ◽  
Vol 2018 ◽  
pp. 1-6
Author(s):  
Adriana A. Almeida-Apolonio ◽  
Wellinton J. Cupozak-Pinheiro ◽  
Vagner M. Berres ◽  
Fabiana G. S. Dantas ◽  
Terezinha I. E. Svidzinski ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Biofilm Formation ◽  
Antifungal Agents ◽  
Ethanolic Extract ◽  
Etiologic Agent ◽  
Antifungal Drugs ◽  
Antibiofilm Activity ◽  
Colony Forming Units ◽  
Checkerboard Assay ◽  
Serious Disease

Cryptococcus gattiiis an etiologic agent of cryptococcosis and a serious disease that affects immunocompromised and immunocompetent patients worldwide. The therapeutic arsenal used to treat cryptococcosis is limited to a few antifungal agents, and the ability ofC. gattiito form biofilms may hinder treatment and decrease its susceptibility to antifungal agents. The objective of this study was to evaluate the antifungal and antibiofilm activities of an ethanolic extract ofCochlospermum regium(Schrank) Pilger leaves againstC. gattii. The antifungal activity was assessed by measuring the minimum inhibitory concentration (MIC) using the broth microdilution technique and interaction of the extract with fluconazole was performed of checkerboard assay. The antibiofilm activity of the extract was evaluated in 96-well polystyrene microplates, and the biofilms were quantified by counting colony forming units. The extract showed antifungal activity at concentrations of 62.5 to 250μg/mL and when the extract was evaluated in combination with fluconazole,C. gattiiwas inhibited at sub-MIC levels. The antibiofilm activity of the extract againstC. gattiiwas observed both during biofilm formation and on an already established biofilm. The results showed that the ethanolic extract of the leaves ofC. regiumshows promise for the development of antifungal drugs to treat cryptococcosis and to combatC. gattiibiofilms.

Antibiofilm activity of antifungal drugs, including the novel drug olorofim, against Lomentospora prolificans

2020 ◽  
Author(s):  
Lisa Kirchhoff ◽  
Silke Dittmer ◽  
Ann-Kathrin Weisner ◽  
Jan Buer ◽  
Peter-Michael Rath ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Biofilm Formation ◽  
Laser Scanning ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Pathogenic Fungus ◽  
Antifungal Drugs ◽  
Laser Scanning Microscopy ◽  
Confocal Laser ◽  
Antibiofilm Activity

Abstract Objectives Patients with immunodeficiency or cystic fibrosis frequently suffer from respiratory fungal infections. In particular, biofilm-associated fungi cause refractory infection manifestations, linked to increased resistance to anti-infective agents. One emerging filamentous fungus is Lomentospora prolificans. Here, the biofilm-formation capabilities of L. prolificans isolates were investigated and the susceptibility of biofilms to various antifungal agents was analysed. Methods Biofilm formation of L. prolificans (n = 11) was estimated by crystal violet stain and antibiofilm activity was additionally determined via detection of metabolically active biofilm using an XTT assay. Amphotericin B, micafungin, voriconazole and olorofim were compared with regard to their antibiofilm effects when added prior to adhesion, after adhesion and on mature and preformed fungal biofilms. Imaging via confocal laser scanning microscopy was carried out to demonstrate the effect of drug treatment on the fungal biofilm. Results Antibiofilm activities of the tested antifungal agents were shown to be most effective on adherent cells whilst mature biofilm was the most resistant. The most promising antibiofilm effects were detected with voriconazole and olorofim. Olorofim showed an average minimum biofilm eradication concentration (MBEC) of 0.06 mg/L, when added prior to and after adhesion. The MBECs of voriconazole were ≤4 mg/L. On mature biofilm the MBECs of olorofim and voriconazole were higher than the previously determined MICs against planktonic cultures. In contrast, amphotericin B and especially micafungin did not exhibit sufficient antibiofilm activity against L. prolificans. Conclusions To our knowledge, this is the first study demonstrating the antibiofilm potential of olorofim against the human pathogenic fungus L. prolificans.

Terpinen-4-ol inhibits the growth of Sporothrix schenckii complex and exhibits synergism with antifungal agents

2019 ◽  
Vol 14 (14) ◽  
pp. 1221-1233 ◽  
Author(s):  
Raimunda SN Brilhante ◽  
Vandbergue S Pereira ◽  
Jonathas S Oliveira ◽  
Anderson M Rodrigues ◽  
Zoilo P de Camargo ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Antifungal Agents ◽  
Sporothrix Schenckii ◽  
Potential Effect ◽  
Antibiofilm Activity ◽  
Minimal Inhibitory Concentrations ◽  
Violet Crystal ◽  
Pharmacological Interactions ◽  
Reduction Assay ◽  
Checkerboard Assay

Aim: This study investigated the effect of terpinen-4-ol against Sporothrix schenckii complex and its interactions with antifungals. Materials & methods: The antifungal activity of terpinen-4-ol was evaluated by broth microdilution. The potential effect on cellular ergosterol concentration was evaluated by spectrophotometry. The antibiofilm activity was evaluated by violet crystal staining and XTT reduction assay. The potential pharmacological interactions with antifungals were evaluated by the checkerboard assay. Results: terpinen-4-ol (T-OH) showed minimal inhibitory concentrations ranging from 4 to 32 mg/l decreasing cellular ergosterol content and presented a SMIC ranging from 64 to 1024 mg/l for Sporothrix spp. The combinations of T-OH with itraconazole or terbinafine were synergistic. Conclusion: T-OH has antifungal activity against Sporothrix spp. and acts synergistically with standard antifungals.

scholarly journals Identification of a Phenylthiazole Small Molecule with Dual Antifungal and Antibiofilm Activity Against Candida albicans and Candida auris

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Haroon Mohammad ◽  
Hassan E. Eldesouky ◽  
Tony Hazbun ◽  
Abdelrahman S. Mayhoub ◽  
Mohamed N. Seleem
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Small Molecules ◽  
Fungicidal Activity ◽  
Antifungal Agents ◽  
Limit Of Detection ◽  
Antifungal Drugs ◽  
Antibiofilm Activity ◽  
Drug Resistant ◽  
Candida Auris

AbstractCandida 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.

scholarly journals Antibacterial and Antifungal Activity of Clove Extract (Syzygium Aromaticum): Review

2021 ◽  
Vol 2 (2) ◽  
pp. 93-103
Author(s):  
Nathaniel Hiwandika ◽  
Susana Elya Sudrajat ◽  
Ika Rahayu
Keyword(s):  
Antifungal Activity ◽  
Antifungal Agents ◽  
Ethanolic Extract ◽  
Therapeutic Effects ◽  
Syzygium Aromaticum ◽  
Antibacterial And Antifungal Activity ◽  
E Coli ◽  
Clove Essential Oil ◽  
Clove Extract ◽  
Antibacterial And Antifungal

Cloves is one of the native Indonesian plants and is used in many aspects of life. Cloves are used in multiple industries and as detergents, soaps, perfumes, food seasonings, aromatherapy, etc. Cloves are mainly used for ingredients in kretek cigarettes in Indonesia. Various studies of cloves reported they have good pharmacological and therapeutic effects. The main compounds of clove extract are eugenol and β-caryophyllene, which are powerful antibacterial and antifungal agents. The clove ethanolic extract showed the activity to inhibit Gram positive and negative bacteria such as B. cereus, S. aureus, E. coli, P. aeruginosa, S. pneumoniae, S. aureus, S. epidermidis, A. hydrophila, K. pneumoniae, P. gingivalis, and P. mirabilis. Clove essential oil has shown the ability to inhibit the growth of V. inaequalis, C. albicans, C. glabrata, and C. tropicalis. Cloves extract can be used as an essential ingredient of various medicines. However, it requires further research and trials.

scholarly journals Darunavir inhibits Cryptococcus neoformans/Cryptococcus gattii species complex growth and increases the susceptibility of biofilms to antifungal drugs

2020 ◽  
Vol 69 (6) ◽  
pp. 830-837
Author(s):  
Raimunda Sâmia Nogueira Brilhante ◽  
José Alexandre Telmos Silva ◽  
Géssica dos Santos Araújo ◽  
Vandbergue Santos Pereira ◽  
Wilker Jose Perez Gotay ◽  
...  
Keyword(s):  
Cryptococcus Neoformans ◽  
Amphotericin B ◽  
Metabolic Activity ◽  
Biofilm Formation ◽  
Species Complex ◽  
Cryptococcus Gattii ◽  
Antifungal Drugs ◽  
Planktonic Cells ◽  
Species Activity ◽  
Checkerboard Assay

Introduction. Cryptococcus species are pathogens commonly associated with cases of meningoencephalitis in individuals who are immunosuppressed due to AIDS. Aim. The aim was to evaluate the effects of the antiretroviral darunavir alone or associated with fluconazole, 5-flucytosine and amphotericin B against planktonic cells and biofilms of Cryptococcus species. Methodology. Susceptibility testing of darunavir and the common antifungals against 12 members of the Cryptococcus neoformans/Cryptococcus gattii species complex was evaluated by broth microdilution. The interaction between darunavir and antifungals against planktonic cells was tested by a checkerboard assay. The effects of darunavir against biofilm metabolic activity and biomass were evaluated by the XTT reduction assay and crystal violet staining, respectively. Results. Darunavir combined with amphotericin B showed a synergistic interaction against planktonic cells. No antagonistic interaction was observed between darunavir and the antifungals used. All Cryptococcus species strains were strong biofilm producers. Darunavir alone reduced biofilm metabolic activity and biomass when added during and after biofilm formation (P<0.05). The combination of darunavir with antifungals caused a significant reduction in biofilm metabolic activity and biomass when compared to darunavir alone (P<0.05). Conclusion. Darunavir presents antifungal activity against planktonic cells of Cryptococcus species and synergism with amphotericin B. In addition, darunavir led to reduced biofilm formation and showed activity against mature biofilms of Cryptococcus species. Activity of the antifungals against mature biofilms was enhanced in the presence of darunavir.

scholarly journals Plant-Derived Substances in the Fight Against Infections Caused by Candida Species

2020 ◽  
Vol 21 (17) ◽  
pp. 6131
Author(s):  
Ibeth Guevara-Lora ◽  
Grazyna Bras ◽  
Justyna Karkowska-Kuleta ◽  
Miriam González-González ◽  
Kinga Ceballos ◽  
...  
Keyword(s):  
Candida Species ◽  
Biofilm Formation ◽  
Defense Mechanisms ◽  
Antifungal Agents ◽  
Standard Treatment ◽  
Antifungal Drugs ◽  
Host Immune System ◽  
Plant Metabolites ◽  
Fungal Cell ◽  
Mucosal Surfaces

Yeast-like fungi from the Candida genus are predominantly harmless commensals that colonize human skin and mucosal surfaces, but under conditions of impaired host immune system change into dangerous pathogens. The pathogenicity of these fungi is typically accompanied by increased adhesion and formation of complex biofilms, making candidal infections challenging to treat. Although a variety of antifungal drugs have been developed that preferably attack the fungal cell wall and plasma membrane, these pathogens have acquired novel defense mechanisms that make them resistant to standard treatment. This causes an increase in the incidence of candidiasis and enforces the urgent need for an intensified search for new specifics that could be helpful, alone or synergistically with traditional drugs, for controlling Candida pathogenicity. Currently, numerous reports have indicated the effectiveness of plant metabolites as potent antifungal agents. These substances have been shown to inhibit growth and to alter the virulence of different Candida species in both the planktonic and hyphal form and during the biofilm formation. This review focuses on the most recent findings that provide evidence of decreasing candidal pathogenicity by different substances of plant origin, with a special emphasis on the mechanisms of their action. This is a particularly important issue in the light of the currently increasing frequency of emerging Candida strains and species resistant to standard antifungal treatment.

scholarly journals High Efficiency Drug Repurposing Design for New Antifungal Agents

2019 ◽  
Vol 2 (2) ◽  
pp. 31 ◽  
Author(s):  
Jong H. Kim ◽  
Kathleen L. Chan ◽  
Luisa W. Cheng ◽  
Lisa A. Tell ◽  
Barbara A. Byrne ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Fungal Pathogens ◽  
Antifungal Agents ◽  
High Efficiency ◽  
Intervention Strategy ◽  
Drug Repurposing ◽  
Antifungal Drugs ◽  
Antifungal Drug ◽  
Alternative Intervention ◽  
Combined Application

Current antifungal interventions have often limited efficiency in treating fungal pathogens, particularly those resistant to commercial drugs or fungicides. Antifungal drug repurposing is an alternative intervention strategy, whereby new utility of various marketed, non-antifungal drugs could be repositioned as novel antifungal agents. In this study, we investigated “chemosensitization” as a method to improve the efficiency of antifungal drug repurposing, wherein combined application of a second compound (viz., chemosensitizer) with a conventional, non-antifungal drug could greatly enhance the antifungal activity of the co-applied drug. Redox-active natural compounds or structural derivatives, such as thymol (2-isopropyl-5-methylphenol), 4-isopropyl-3-methylphenol, or 3,5-dimethoxybenzaldehyde, could serve as potent chemosensitizers to enhance antifungal activity of the repurposed drug bithionol. Of note, inclusion of fungal mutants, such as antioxidant mutants, could also facilitate drug repurposing efficiency, which is reflected in the enhancement of antifungal efficacy of bithionol. Bithionol overcame antifungal (viz., fludioxonil) tolerance of the antioxidant mutants of the human/animal pathogen Aspergillus fumigatus. Altogether, our strategy can lead to the development of a high efficiency drug repurposing design, which enhances the susceptibility of pathogens to drugs, reduces time and costs for new antifungal development, and abates drug or fungicide resistance.

scholarly journals Combination of antifungal drugs and protease inhibitors prevent Candida albicans biofilm formation and disrupt mature biofilms

2020 ◽  
Author(s):  
Matthew B. Lohse ◽  
Megha Gulati ◽  
Charles S. Craik ◽  
Alexander D. Johnson ◽  
Clarissa J. Nobile
Keyword(s):  
Candida Albicans ◽  
Protease Inhibitors ◽  
Amphotericin B ◽  
Biofilm Formation ◽  
Antifungal Agents ◽  
Antifungal Drugs ◽  
Aspartyl Protease ◽  
Abiotic Surfaces ◽  
Drug Concentrations ◽  
Aspartyl Protease Inhibitors

AbstractBiofilms formed by the fungal pathogen Candida albicans are resistant to many of the antifungal agents commonly used in the clinic. Previous reports suggest that protease inhibitors, specifically inhibitors of aspartyl proteases, could be effective antibiofilm agents. We screened three protease inhibitor libraries, containing a total of 80 compounds for the abilities to prevent C. albicans biofilm formation and to disrupt mature biofilms. The compounds were screened individually and in the presence of subinhibitory concentrations of the most commonly prescribed antifungal agents for Candida infections: fluconazole, amphotericin B, or caspofungin. Although few of the compounds affected biofilms on their own, seven aspartyl protease inhibitors inhibited biofilm formation when combined with amphotericin B or caspofungin. Furthermore, nine aspartyl protease inhibitors disrupted mature biofilms when combined with caspofungin. These results suggest that the combination of standard antifungal agents together with specific protease inhibitors may be useful in the prevention and treatment of C. albicans biofilm infections.ImportanceCandida albicans is one of the most common pathogens of humans. C. albicans forms biofilms, structured communities of cells several hundred microns thick, on both biotic and abiotic surfaces. These biofilms are typically resistant to antifungal drugs at the concentrations that are normally effective against free-floating cells, thus requiring treatment with higher drug concentrations that often have significant side effects. Here, we show that certain combinations of existing antifungal agents with protease inhibitors, including several drugs already commonly used to treat HIV patients, are effective at inhibiting biofilm formation by C. albicans and/or at disrupting mature C. albicans biofilms.

scholarly journals Antifungal activity of various plant oils against yeast isolates from ICU patients

2017 ◽  
Vol 5 (7) ◽  
pp. 3227
Author(s):  
Akansha Suman ◽  
Sapna Chauhan ◽  
Suman Lata ◽  
Rajeev K. Sharma
Keyword(s):  
Antifungal Activity ◽  
Antifungal Agents ◽  
Tertiary Care ◽  
Antifungal Drugs ◽  
Diffusion Method ◽  
Clinical Samples ◽  
Plant Oils ◽  
Clove Oil ◽  
Icu Patients ◽  
Long Term Treatment

Background: To evaluate the in-vitro antifungal activity of various essential plant oils against yeast species.Methods: The present study was a prospective study conducted in Department of Microbiology along with Department of Pharmacology at Tertiary care teaching hospital. Various clinical samples from ICU patients were inoculated on Sabourauds Dextrose Agar (SDA) in accordance with the standard methods. Yeast isolates were recovered and identified as per standard recommended procedure. The antifungal activity of plant oils against these isolated yeasts was determined using disc diffusion method. The results were interpreted as <9mm-inactive, 9-12mm-partially active, 13-18mm-very active. Fluconazole and Itraconazole were taken as control drugs.Results: The various yeast isolated were C. albicans, C. tropicals, C. krusei, C. glabrata, C. gulliermondi, C. keyfr, Cryptococcus and Tricosporon. Among essential plant oils, Cinnamon oil and clove oil showed high activity against all isolated yeast species. Olive oil showed least antifungal activity. Fluconazole was resistant in all yeast isolates, while Itraconazole was sensitive to all yeast isolates. Sensitivity of cinnamon and clove oil was statistically significant than Itraconazole.Conclusions: To conclude present study shows the potential of essential plant oils as newer therapeutic alternatives to antifungal drugs. These may be used in combination with antifungal agents to overcome drug resistance, adverse effects and in shortening the long-term treatment with antifungal drugs. Thus, these essential plant oils can be used in future as antifungal agents in azoles resistant strains.

scholarly journals Screening Repurposing Libraries for Identification of Drugs with Novel Antifungal Activity

2020 ◽  
Vol 64 (9) ◽  
Author(s):  
Gina Wall ◽  
Jose L. Lopez-Ribot
Keyword(s):  
Antifungal Activity ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Alternative Pathway ◽  
Drug Repurposing ◽  
Pathogenic Fungi ◽  
Multidrug Resistant ◽  
Modern Medicine ◽  
Antifungal Drugs ◽  
Promising Alternative

ABSTRACT Fungal organisms are ubiquitous in nature, and progress of modern medicine is creating an expanding number of severely compromised patients susceptible to a variety of opportunistic fungal infections. These infections are difficult to diagnose and treat, leading to high mortality rates. The limited antifungal arsenal, the toxicity of current antifungal drugs, the development of resistance, and the emergence of new multidrug-resistant fungi, all highlight the urgent need for new antifungal agents. Unfortunately, the development of a novel antifungal is a rather long and expensive proposition, and no new classes of antifungal agents have reached the market in the last 2 decades. Drug repurposing, or finding new indications for old drugs, represents a promising alternative pathway to drug development that is particularly appealing within the academic environment. In the last few years, there has been a growing interest in repurposing approaches in the antifungal arena, with multiple groups of investigators having performed screenings of different repurposing libraries against different pathogenic fungi in search for drugs with previously unrecognized antifungal effects. Overall, these repurposing efforts may lead to the fast deployment of drugs with novel antifungal activity, which can rapidly bring benefits to patients, while at the same time reducing health care costs.

Sign in / Sign up

Export Citation Format

Share Document