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 Chitinases Are Essential for Sexual Development but Not Vegetative Growth in Cryptococcus neoformans

2009 ◽  
Vol 8 (11) ◽  
pp. 1692-1705 ◽  
Author(s):  
Lorina G. Baker ◽  
Charles A. Specht ◽  
Jennifer K. Lodge
Keyword(s):  
Cell Wall ◽  
Sexual Reproduction ◽  
Cryptococcus Neoformans ◽  
Vegetative Growth ◽  
Cell Walls ◽  
Cell Structure ◽  
Complex Structure ◽  
Hydrolytic Enzymes ◽  
Fungal Cell ◽  
Fungal Cell Walls

ABSTRACT Cryptococcus neoformans is an opportunistic pathogen that mainly infects immunocompromised individuals. The fungal cell wall of C. neoformans is an excellent target for antifungal therapies since it is an essential organelle that provides cell structure and integrity. Importantly, it is needed for localization or attachment of known virulence factors, including melanin, phospholipase, and the polysaccharide capsule. The polysaccharide fraction of the cryptococcal cell wall is a complex structure composed of chitin, chitosan, and glucans. Chitin is an indispensable component of many fungal cell walls that contributes significantly to cell wall strength and integrity. Fungal cell walls are very dynamic, constantly changing during cell division and morphogenesis. Hydrolytic enzymes, such as chitinases, have been implicated in the maintenance of cell wall plasticity and separation of the mother and daughter cells at the bud neck during vegetative growth in yeast. In C. neoformans we identified four predicted endochitinases, CHI2, CHI21, CHI22, and CHI4, and a predicted exochitinase, hexosaminidase, HEX1. Enzymatic analysis indicated that Chi2, Chi22, and Hex1 actively degraded chitinoligomeric substrates. Chi2 and Hex1 activity was associated mostly with the cellular fraction, and Chi22 activity was more prominent in the supernatant. The enzymatic activity of Hex1 increased when grown in media containing only N-acetylglucosamine as a carbon source, suggesting that its activity may be inducible by chitin degradation products. Using a quadruple endochitinase deletion strain, we determined that the endochitinases do not affect the growth or morphology of C. neoformans during asexual reproduction. However, mating assays indicated that Chi2, Chi21, and Chi4 are each involved in sexual reproduction. In summary, the endochitinases were found to be dispensable for routine vegetative growth but not sexual reproduction.

scholarly journals The newly synthesized thiazole derivatives as potential antifungal compounds against Candida albicans

2021 ◽  
Author(s):  
Anna Biernasiuk ◽  
Anna Berecka-Rycerz ◽  
Anna Gumieniczek ◽  
Maria Malm ◽  
Krzysztof Z. Łączkowski ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Antifungal Activity ◽  
Cell Membrane ◽  
Mode Of Action ◽  
Thiazole Derivatives ◽  
Fungal Cell ◽  
Erythrocyte Lysis ◽  
Low Cytotoxicity ◽  
High Antifungal Activity

Abstract Recently, the occurrence of candidiasis has increased dramatically, especially in immunocompromised patients. Additionally, their treatment is often ineffective due to the resistance of yeasts to antimycotics. Therefore, there is a need to search for new antifungals. A series of nine newly synthesized thiazole derivatives containing the cyclopropane system, showing promising activity against Candida spp., has been further investigated. We decided to verify their antifungal activity towards clinical Candida albicans isolated from the oral cavity of patients with hematological malignancies and investigate the mode of action on fungal cell, the effect of combination with the selected antimycotics, toxicity to erythrocytes, and lipophilicity. These studies were performed by the broth microdilution method, test with sorbitol and ergosterol, checkerboard technique, erythrocyte lysis assay, and reversed phase thin-layer chromatography, respectively. All derivatives showed very strong activity (similar and even higher than nystatin) against all C. albicans isolates with minimal inhibitory concentration (MIC) = 0.008–7.81 µg/mL Their mechanism of action may be related to action within the fungal cell wall structure and/or within the cell membrane. The interactions between the derivatives and the selected antimycotics (nystatin, chlorhexidine, and thymol) showed additive effect only in the case of combination some of them and thymol. The erythrocyte lysis assay confirmed the low cytotoxicity of these compounds as compared to nystatin. The high lipophilicity of the derivatives was related with their high antifungal activity. The present studies confirm that the studied thiazole derivatives containing the cyclopropane system appear to be a very promising group of compounds in treatment of infections caused by C. albicans. However, this requires further studies in vivo. Key points • The newly thiazoles showed high antifungal activity and some of them — additive effect in combination with thymol. • Their mode of action may be related with the influence on the structure of the fungal cell wall and/or the cell membrane. • The low cytotoxicity against erythrocytes and high lipophilicity of these derivatives are their additional good properties. Graphical abstract

scholarly journals Jerveratrum-Type Steroidal Alkaloids Inhibit β-1,6-Glucan Biosynthesis in Fungal Cell Walls

2022 ◽  
Author(s):  
Karen Kubo ◽  
Kaori Itto-Nakama ◽  
Shinsuke Ohnuki ◽  
Yoko Yashiroda ◽  
Sheena C. Li ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Cell Walls ◽  
Therapeutic Agents ◽  
Antifungal Drugs ◽  
Steroidal Alkaloids ◽  
Fungal Cell ◽  
Content Type ◽  
Fungal Cell Walls

Non- Candida albicans Candida species (NCAC) are on the rise as a cause of mycosis. Many antifungal drugs are less effective against NCAC, limiting the available therapeutic agents.

scholarly journals Antifungal Activity of Rye (Secale cereale) Seed Chitinases: the Different Binding Manner of Class I and Class II Chitinases to the Fungal Cell Walls

2002 ◽  
Vol 66 (5) ◽  
pp. 970-977 ◽  
Author(s):  
Toki TAIRA ◽  
Takayuki OHNUMA ◽  
Takeshi YAMAGAMI ◽  
Yoichi ASO ◽  
Masatsune ISHIGURO ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Secale Cereale ◽  
Cell Walls ◽  
Class Ii ◽  
Class I ◽  
Fungal Cell ◽  
Fungal Cell Walls

scholarly journals Localization of chitin in algal and fungal cell walls by light and electron microscopy.

1978 ◽  
Vol 26 (10) ◽  
pp. 782-791 ◽  
Author(s):  
N L Pearlmutter ◽  
C A Lembi
Keyword(s):  
Electron Microscopy ◽  
Cell Wall ◽  
Acetic Acid ◽  
Electron Microscope ◽  
Cell Walls ◽  
Potassium Hydroxide ◽  
Light And Electron Microscopy ◽  
Fungal Cell ◽  
Blastocladiella Emersonii ◽  
Fungal Cell Walls

Chitin was visualized in cell walls after hydrolysis with potassium hydroxide and subsequent postfixation of the deacetylated polysaccharide (chitosan) in OsO4. Areas of chitin deposition appeared dark borwn by light microscopy and electron dense in the electron microscope. With this method, the presence of chitin was demonstrated in the cell walls of the green alga Pithophora oedogonia (Montagne) Wittrock and two fungi, Ceratocystis ulmi Buism. (C. Moreau) and Blastocladiella emersonii Cantino and Hyatt. Most of the chitin in P. oedogonia ws found in the crosswall disk and small amounts occurred in the outer longitudinal walls. The septal disk of C. ulmi also contained chitin, but significant amounts were present in the inner and outer regions of longitudinal walls as well. Chitin was present throughout the walls of B. emersonii. Small amounts of chitin were not easily demonstrated by this technique, but removal of chitosan by exposure to dilute acetic acid before osmium fixation disrupted cell wall integrity, suggesting that small amounts of the structural polysaccharide had been removed.

scholarly journals FsFKS1, the 1,3-β-Glucan Synthase from the Caspofungin-Resistant Fungus Fusarium solani

2006 ◽  
Vol 5 (7) ◽  
pp. 1036-1042 ◽  
Author(s):  
Young-sil Ha ◽  
Sarah F. Covert ◽  
Michelle Momany
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Fusarium Solani ◽  
Cell Walls ◽  
Clinical Isolates ◽  
Fungal Cell ◽  
Spore Viability ◽  
Glucan Synthase ◽  
Main Components ◽  
Sensitive Fungus

ABSTRACT The cell wall, a mesh of carbohydrates and proteins, shapes and protects the fungal cell. The enzyme responsible for the synthesis of one of the main components of the fungal wall, 1,3-β-glucan synthase, is targeted by the antifungal caspofungin acetate (CFA). Clinical isolates of Candida albicans and Aspergillus fumigatus are much more sensitive to CFA than clinical isolates of Fusarium species. To better understand CFA resistance in Fusarium species, we cloned and sequenced FsFKS1, which encodes the Fusarium solani f. sp. pisi β(1,3)-d-glucan synthase, used RNA interference to reduce its expression and complemented deletion of the essential fks gene of the CFA-sensitive fungus A. fumigatus with FsFKS1. Reduction of the FsFKS1 message in F. solani f. sp. pisi reduced spore viability and caused lysis of spores and hyphae, consistent with cell wall defects. Compensating for the loss of A. fumigatus fks1 with FsFKS1 caused only a modest increase in the tolerance of A. fumigatus for CFA. Our results suggest that FsFKS1 is required for the proper construction of F. solani cell walls and that the resistance of F. solani to CFA is at best only partially due to resistance of the FsFKS1 enzyme to this antifungal agent.

Melanin deposition in the hyphae of a species of Phomopsis

1975 ◽  
Vol 21 (4) ◽  
pp. 442-452 ◽  
Author(s):  
D. H. Ellis ◽  
D. A. Griffiths
Keyword(s):  
Cell Wall ◽  
Surface Analysis ◽  
Cell Walls ◽  
Lytic Enzymes ◽  
Fungal Cell ◽  
Ionizing Radiations ◽  
Dopa Melanin ◽  
Fungal Cell Walls ◽  
Cellular Organelles

Hyaline hyphae of Phomopsis become pigmented when exposed to short periods of light. Pigment was deposited in the form of melanin granules both within the cell wall and within mucilaginous excrescences that were developed irregularly over the hyphal surface. Analysis of the pigment showed it to have properties similar to that of "Dopa" melanin and to pigments previously isolated from fungal cell walls. Lysis of both hyaline and pigmented hyphal walls by means of lytic enzymes was minimal. It is suggested that the major role of melanin in this fungus is the protection of cellular organelles from harmful ionizing radiations.

scholarly journals An Assessment of Infrared Spectra as Indicators of Fungal Cell Wall Composition

1970 ◽  
Vol 23 (2) ◽  
pp. 345 ◽  
Author(s):  
A JMichell ◽  
G Sourfield
Keyword(s):  
Cell Wall ◽  
Infrared Spectroscopy ◽  
Infrared Spectra ◽  
Cell Walls ◽  
Cell Wall Composition ◽  
Fungal Cell Wall ◽  
Fungal Cell ◽  
Chemical Treatments ◽  
Wall Components ◽  
Fungal Cell Walls

Infrared spectroscopy is assessed as a technique for identifying polymers derived from fungal cell walls, both as isolated materials and in mixtures with one another. The technique is then applied to a study of the composition of fungal cell walls and the conclusion reached that infrared spectra provide a rapid and valuable indication of the major components of such walls. They can also be used to follow the effect of chemical treatments designed to separate major wall components.

scholarly journals Disarming Fungal Pathogens:Bacillus safensisInhibits Virulence Factor Production and Biofilm Formation byCryptococcus neoformansandCandida albicans

mBio ◽  
2017 ◽  
Vol 8 (5) ◽  
Author(s):  
François L. Mayer ◽  
James W. Kronstad
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Cryptococcus Neoformans ◽  
Virulence Factors ◽  
Virulence Factor ◽  
Biofilm Formation ◽  
Fungal Pathogens ◽  
Soil Bacterium ◽  
Fungal Cell ◽  
Virulence Factor Production

ABSTRACTBacteria interact with each other in nature and often compete for limited nutrient and space resources. However, it is largely unknown whether and how bacteria also interact with human fungal pathogens naturally found in the environment. Here, we identified a soil bacterium,Bacillus safensis, which potently blocked several keyCryptococcus neoformansvirulence factors, including formation of the antioxidant pigment melanin and production of the antiphagocytic polysaccharide capsule. The bacterium also inhibitedde novocryptococcal biofilm formation but had only modest inhibitory effects on already formed biofilms or planktonic cell growth. The inhibition of fungal melanization was dependent on direct cell contact and live bacteria.B. safensisalso had anti-virulence factor activity against another major human-associated fungal pathogen,Candida albicans. Specifically, dual-species interaction studies revealed that the bacterium strongly inhibitedC. albicansfilamentation and biofilm formation. In particular,B. safensisphysically attached to and degraded candidal filaments. Through genetic and phenotypic analyses, we demonstrated that bacterial chitinase activity against fungal cell wall chitin is a factor contributing to the antipathogen effect ofB. safensis.IMPORTANCEPathogenic fungi are estimated to contribute to as many human deaths as tuberculosis or malaria. Two of the most common fungal pathogens,Cryptococcus neoformansandCandida albicans, account for up to 1.4 million infections per year with very high mortality rates. Few antifungal drugs are available for treatment, and development of novel therapies is complicated by the need for pathogen-specific targets. Therefore, there is an urgent need to identify novel drug targets and new drugs. Pathogens use virulence factors during infection, and it has recently been proposed that targeting these factors instead of the pathogen itself may represent a new approach to develop antimicrobials. Here, we identified a soil bacterium that specifically blocked virulence factor production and biofilm formation byC. neoformansandC. albicans. We demonstrate that the bacterial antipathogen mechanism is based in part on targeting the fungal cell wall, a structure not found in human cells.

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