scholarly journals Candida albicans, Cryptococcus neoformans or Aspergillus fumigatus Induces an Antifungal Activity in Mouse Serum, which is Different from Transferrin

2009 ◽  
Vol 71 (11) ◽  
pp. 1459-1464
Author(s):  
Ken-ichi OKAZAKI ◽  
Masahiro ASAKURA ◽  
Norihiko SUGIMOTO ◽  
Atsushi HINENOYA ◽  
Shinji YAMASAKI
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Aspergillus Fumigatus ◽  
Cryptococcus Neoformans ◽  
Mouse Serum

scholarly journals Dectin-2-Targeted Antifungal Liposomes Exhibit Enhanced Efficacy

mSphere ◽  
2019 ◽  
Vol 4 (5) ◽  
Author(s):  
Suresh Ambati ◽  
Emma C. Ellis ◽  
Jianfeng Lin ◽  
Xiaorong Lin ◽  
Zachary A. Lewis ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Aspergillus Fumigatus ◽  
Effective Dose ◽  
Cryptococcus Neoformans ◽  
Amphotericin B ◽  
Antifungal Drugs ◽  
Extracellular Matrices ◽  
Content Type ◽  
Order Of Magnitude ◽  
Life Threatening

ABSTRACT Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus cause life-threatening candidiasis, cryptococcosis, and aspergillosis, resulting in several hundred thousand deaths annually. The patients at the greatest risk of developing these life-threatening invasive fungal infections have weakened immune systems. The vulnerable population is increasing due to rising numbers of immunocompromised individuals as a result of HIV infection or immunosuppressed individuals receiving anticancer therapies and/or stem cell or organ transplants. While patients are treated with antifungals such as amphotericin B, all antifungals have serious limitations due to lack of sufficient fungicidal effect and/or host toxicity. Even with treatment, 1-year survival rates are low. We explored methods of increasing drug effectiveness by designing fungicide-loaded liposomes specifically targeted to fungal cells. Most pathogenic fungi are encased in cell walls and exopolysaccharide matrices rich in mannans. Dectin-2 is a mammalian innate immune membrane receptor that binds as a dimer to mannans and signals fungal infection. We coated amphotericin-loaded liposomes with monomers of Dectin-2’s mannan-binding domain, sDectin-2. sDectin monomers were free to float in the lipid membrane and form dimers that bind mannan substrates. sDectin-2-coated liposomes bound orders of magnitude more efficiently to the extracellular matrices of several developmental stages of C. albicans, C. neoformans, and A. fumigatus than untargeted control liposomes. Dectin-2-coated amphotericin B-loaded liposomes reduced the growth and viability of all three species more than an order of magnitude more efficiently than untargeted control liposomes and dramatically decreased the effective dose. Future efforts focus on examining pan-antifungal targeted liposomal drugs in animal models of fungal diseases. IMPORTANCE Invasive fungal diseases caused by Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus have mortality rates ranging from 10 to 95%. Individual patient costs may exceed $100,000 in the United States. All antifungals in current use have serious limitations due to host toxicity and/or insufficient fungal cell killing that results in recurrent infections. Few new antifungal drugs have been introduced in the last 2 decades. Hence, there is a critical need for improved antifungal therapeutics. By targeting antifungal-loaded liposomes to α-mannans in the extracellular matrices secreted by these fungi, we dramatically reduced the effective dose of drug. Dectin-2-coated liposomes loaded with amphotericin B bound 50- to 150-fold more strongly to C. albicans, C. neoformans, and A. fumigatus than untargeted liposomes and killed these fungi more than an order of magnitude more efficiently. Targeting drug-loaded liposomes specifically to fungal cells has the potential to greatly enhance the efficacy of most antifungal drugs.

scholarly journals Novel Antifungal Compounds Discovered in Medicines for Malaria Venture’s Malaria Box

mSphere ◽  
2018 ◽  
Vol 3 (2) ◽  
Author(s):  
Eric H. Jung ◽  
David J. Meyers ◽  
Jürgen Bosch ◽  
Arturo Casadevall
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Cryptococcus Neoformans ◽  
Fungal Pathogens ◽  
Pathogenic Fungi ◽  
Cryptococcus Gattii ◽  
Antifungal Drugs ◽  
Resistant Bacteria ◽  
Animal Cells ◽  
Malaria Box

ABSTRACTSimilarities in fungal and animal cells make antifungal discovery efforts more difficult than those for other classes of antimicrobial drugs. Currently, there are only three major classes of antifungal drugs used for the treatment of systemic fungal diseases: polyenes, azoles, and echinocandins. Even in situations where the offending fungal organism is susceptible to the available drugs, treatment courses can be lengthy and unsatisfactory, since eradication of infection is often very difficult, especially in individuals with impaired immunity. Consequently, there is a need for new and more effective antifungal drugs. We have identified compounds with significant antifungal activity in the Malaria Box (Medicines for Malaria Ventures, Geneva, Switzerland) that have higher efficacy than some of the currently used antifungal drugs. Our best candidate, MMV665943 (IUPAC name 4-[6-[[2-(4-aminophenyl)-3H-benzimidazol-5-yl]methyl]-1H-benzimidazol-2-yl]aniline), here referred to as DM262, showed 16- to 32-fold-higher activity than fluconazole againstCryptococcus neoformans. There was also significant antifungal activity in other fungal species with known antifungal resistance, such asLomentospora prolificansandCryptococcus gattii. Antifungal activity was also observed against a common fungus,Candida albicans. These results are important because they offer a potentially new class of antifungal drugs and the repurposing of currently available therapeutics.IMPORTANCEMuch like the recent increase in drug-resistant bacteria, there is a rise in antifungal-resistant strains of pathogenic fungi. There is a need for novel and more potent antifungal therapeutics. Consequently, we investigated a mixed library of drug-like and probe-like compounds with activity inPlasmodiumspp. for activity against two common fungal pathogens,Cryptococcus neoformansandCandida albicans, along with two less common pathogenic species,Lomentospora prolificansandCryptococcus gattii. We uncover a previously uncharacterized drug with higher broad-spectrum antifungal activity than some current treatments. Our findings may eventually lead to a compound added to the arsenal of antifungal therapeutics.

scholarly journals Antifungal Activity of the Essential Oil of Echinops kebericho Mesfin: An In Vitro Study

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Tamirat Bekele Beressa ◽  
Serawit Deyno ◽  
Paul E. Alele
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Essential Oil ◽  
Cryptococcus Neoformans ◽  
Antioxidant Properties ◽  
Pathogenic Fungi ◽  
Diffusion Method ◽  
Potential Candidate ◽  
Standard Drug

Background. Echinops kebericho is an endemic medicinal plant in Ethiopia widely used in the treatment of infectious and noninfectious diseases. Essential oils are known for their antibacterial, antifungal, antiviral, insecticidal, and antioxidant properties. This study evaluated the antifungal activity of essential oil from E. kebericho against four common pathogenic fungi and two standard strains. Methods. The essential oil was obtained by hydrodistillation. The antifungal screening was done by agar well diffusion method. Minimal inhibitory concentrations (MICs) were determined by broth microdilution. Minimal fungicidal concentrations (MFCs) were determined by subculturing fungal strains with no visible growth onto a Sabouraud dextrose agar (SDA) plate. Results. Candida albicans and Cryptococcus neoformans were highly sensitive while Aspergillus flavus did not show sensitivity up to 1 mg/ml of essential oil; MICs ranged from 0.083 mg/ml to 0.208 mg/ml. Concentration and fungal species showed significant dose-dependent associations ( p < 0.0001 ) with antifungal activity. The MICs of essential oil were comparable to those of the standard drug (fluconazole) against C. glabrata and C. krusei. The lowest MFC of the essential oil was observed against Candida parapsilosis (0.145 mg/ml) while the highest MFC was against Candida krusei (0.667 mg/ml). Conclusion. Echinops kebericho essential oil showed noteworthy antifungal activity against Cryptococcus neoformans, Candida albicans, and Candida glabrata and could be a potential candidate for further antifungal drug development.

scholarly journals Screening and Antifungal Activity of a β-Carboline Derivative against Cryptococcus neoformans and C. gattii

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Kátia Santana Cruz ◽  
Emerson Silva Lima ◽  
Marcia de Jesus Amazonas da Silva ◽  
Erica Simplício de Souza ◽  
Andreia Montoia ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Antifungal Activity ◽  
Cryptococcus Neoformans ◽  
Active Compound ◽  
Cell Walls ◽  
Human Fibroblasts ◽  
Lead Compound ◽  
Fungal Cell ◽  
Fungal Cell Walls

Background. Cryptococcosis is a fungal disease of bad prognosis due to its pathogenicity and the toxicity of the drugs used for its treatment. The aim of this study was to investigate the medicinal potential of carbazole and β-carboline alkaloids and derivatives against Cryptococcus neoformans and C. gattii. Methods. MICs were established in accordance with the recommendations of the Clinical and Laboratory Standards Institute for alkaloids and derivatives against C. neoformans and C. gattii genotypes VNI and VGI, respectively. A single active compound was further evaluated against C. neoformans genotypes VNII, VNIII, and VNIV, C. gattii genotypes VGI, VGIII, and VGIV, Candida albicans ATCC 36232, for cytotoxicity against the MRC-5 lineage of human fibroblasts and for effects on fungal cells (cell wall, ergosterol, and leakage of nucleic acids). Results. Screening of 11 compounds revealed 8-nitroharmane as a significant inhibitor (MIC 40 μg/mL) of several C. neoformans and C. gattii genotypes. It was not toxic to fibroblasts (IC50 > 50 µg/mL) nor did it alter fungal cell walls or the concentration of ergosterol in C. albicans or C. neoformans. It increased leakage of substances that absorb at 260 nm. Conclusions. The synthetic β-carboline 8-nitroharmane significantly inhibits pathogenic Cryptococcus species and is interesting as a lead compound towards new therapy for Cryptococcus infections.

scholarly journals Chromatin-Mediated Regulation of Genome Plasticity in Human Fungal Pathogens

Genes ◽  
2019 ◽  
Vol 10 (11) ◽  
pp. 855 ◽  
Author(s):  
Buscaino
Keyword(s):  
Candida Albicans ◽  
Aspergillus Fumigatus ◽  
Cryptococcus Neoformans ◽  
Fungal Pathogens ◽  
Environmental Changes ◽  
Structure And Function ◽  
Model Systems ◽  
Genome Plasticity ◽  
And Function ◽  
Heterochromatin Structure

Human fungal pathogens, such as Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans, are a public health problem, causing millions of infections and killing almost half a million people annually. The ability of these pathogens to colonise almost every organ in the human body and cause life-threating infections relies on their capacity to adapt and thrive in diverse hostile host-niche environments. Stress-induced genome instability is a key adaptive strategy used by human fungal pathogens as it increases genetic diversity, thereby allowing selection of genotype(s) better adapted to a new environment. Heterochromatin represses gene expression and deleterious recombination and could play a key role in modulating genome stability in response to environmental changes. However, very little is known about heterochromatin structure and function in human fungal pathogens. In this review, I use our knowledge of heterochromatin structure and function in fungal model systems as a road map to review the role of heterochromatin in regulating genome plasticity in the most common human fungal pathogens: Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans.

scholarly journals Antifungal Activity of Plumericin and Isoplumericin

2011 ◽  
Vol 6 (11) ◽  
pp. 1934578X1100601 ◽  
Author(s):  
Dharmendra Singh ◽  
Umakant Sharma ◽  
Parveen Kumar ◽  
Yogesh K Gupta ◽  
M. P. Dobhal ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Minimum Inhibitory Concentration ◽  
Antifungal Activity ◽  
Cryptococcus Neoformans ◽  
Inhibitory Concentration ◽  
Chloroform Extract ◽  
Drug Candidate ◽  
Minimum Fungicidal Concentration ◽  
In Vitro Antifungal Activity

This study evaluated the in vitro antifungal activity of the chloroform extract of Plumeria bicolor and its phytoconstituents plumericin and isoplumericin against Candida species and Cryptococcus neoformans by measuring the Minimum Inhibitory Concentration (MIC) and Minimum Fungicidal Concentration (MFC). Plumericin's consistently high activity against Candida albicans, C. krusei, C. glabrata, C. tropicalis and Cryptococcus neoformans was more potent than isoplumericin and the standard antifungal drug nystatin suggesting its potential as a drug candidate for candidiasis and cryptococcosis.

In vitro Antifungal Activity of Dihydropyrimidinones/Thiones Against Candida albicans and Cryptococcus neoformans

2020 ◽  
Vol 15 (6) ◽  
pp. 648-655
Author(s):  
Gabriel O. de Azambuja ◽  
Laura Svetaz ◽  
Itamar L. Gonçalves ◽  
Patricia F. Corbelini ◽  
Gilsane L. von Poser ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Drug Design ◽  
Cryptococcus Neoformans ◽  
Biginelli Reaction ◽  
Fungal Growth ◽  
Chemical Library ◽  
Antifungal Effect ◽  
In Vitro Antifungal Activity

Background: Since the Monastrol discovery in 1999 as the first inhibitor of Eg5, functionalized dihydropyrimidinones/thiones (DHPMs) have emerged as prototypes for drug design in different targets. The present work aimed to evaluate the antifungal activity of a chemical library of DHPMs. Methods: The compounds were obtained employing Biginelli reaction. Their antifungal activities were assessed against C. neoformans and C. albicans. Results: The compounds 1-i and 1-k inhibited moderately the fungal growth of C. neoformans, with compound 2-k presenting MIC80 values of 62.5-125 µg·mL-1. Considering activity against C. albicans, the compounds 1-i and 1-n present an MIC50 value of 125-250 µg·mL-1. Conclusion: The changes performed in DHPM scaffold appear to be valuable for generating compounds with potential antifungal effect.

Lipid peroxidation by alveolar macrophages challenged with Cryptococcus neoformans, Candida albicans or Aspergillus fumigatus

2000 ◽  
Vol 38 (6) ◽  
pp. 443-449 ◽  
Author(s):  
N. T. Gross ◽  
K. Hultenby ◽  
S. Mengarelli ◽  
P. Camner ◽  
C. Jarstrand
Keyword(s):  
Lipid Peroxidation ◽  
Candida Albicans ◽  
Aspergillus Fumigatus ◽  
Cryptococcus Neoformans ◽  
Alveolar Macrophages

scholarly journals Biocatalytic Studies of the Furanocoumarins Angelicin and Chalepensin

2007 ◽  
Vol 2 (5) ◽  
pp. 1934578X0700200 ◽  
Author(s):  
Khaled Y. Orabi ◽  
Khalid A. El Sayed
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Cryptococcus Neoformans ◽  
Spectral Data ◽  
Cunninghamella Blakesleeana ◽  
The Absolute ◽  
Lipomyces Lipofer ◽  
Absolute Stereochemistry ◽  
New Metabolites

Bioconversion studies conducted on the furanocoumarins angelicin and chalepensin have revealed that angelicin was metabolized by Lipomyces lipofer (ATCC 10742) to give the corresponding reduced acid 3 and chalepensin was transformed by Cunninghamella blakesleeana (SC-2138) to give the diol metabolite 4. The structures of the new metabolites have been established on the basis of spectral data. The absolute stereochemistry around C-2″ in 4 was confirmed by Horeau's method. Angelicin and chalepensin were shown to possess antifungal activity against Candida albicans and Cryptococcus neoformans.

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