scholarly journals Identification of Antifungal Compounds Active against Candida albicans Using an Improved High-Throughput Caenorhabditis elegans Assay

PLoS ONE ◽  
2009 ◽  
Vol 4 (9) ◽  
pp. e7025 ◽  
Author(s):  
Ikechukwu Okoli ◽  
Jeffrey J. Coleman ◽  
Emmanouil Tempakakis ◽  
W. Frank An ◽  
Edward Holson ◽  
...  
Antibiotics ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 72
Author(s):  
Laura Mena ◽  
Muriel Billamboz ◽  
Rogatien Charlet ◽  
Bérangère Desprès ◽  
Boualem Sendid ◽  
...  

Candidiasis, caused by the opportunistic yeast Candida albicans, is the most common fungal infection today. Resistance of C. albicans to current antifungal drugs has emerged over the past decade leading to the need for novel antifungal agents. Our aim was to select new antifungal compounds by library-screening methods and to assess their antifungal effects against C. albicans. After screening 90 potential antifungal compounds from JUNIA, a chemical library, two compounds, 1-(4-chlorophenyl)-4-((4-chlorophenyl)amino)-3,6-dimethylpyridin-2(1H)-one (PYR) and (Z)-N-(2-(4,6-dimethoxy-1,3,5-triazin-2-yl)vinyl)-4-methoxyaniline (TRI), were identified as having potential antifungal activity. Treatment with PYR and TRI resulted in a significant reduction of C. albicans bioluminescence as well as the number of fungal colonies, indicating rapid fungicidal activity. These two compounds were also effective against clinically isolated fluconazole- or caspofungin-resistant C. albicans strains. PYR and TRI had an inhibitory effect on Candida biofilm formation and reduced the thickness of the mannan cell wall. In a Caenorhabditis elegans infection model, PYR and TRI decreased the mortality of nematodes infected with C. albicans and enhanced the expression of antimicrobial genes that promote C. albicans elimination. Overall, PYR and TRI showed antifungal properties against C. albicans by exerting fungicidal activities and enhancing the antimicrobial gene expression of Caenorhabditis elegans.


2020 ◽  
Vol 16 (1) ◽  
pp. 58-63
Author(s):  
Amrutha Vijayakumar ◽  
Ajith Madhavan ◽  
Chinchu Bose ◽  
Pandurangan Nanjan ◽  
Sindhu S. Kokkal ◽  
...  

Background: Chitin is the main component of fungal, protozoan and helminth cell wall. They help to maintain the structural and functional characteristics of these organisms. The chitin wall is dynamic and is repaired, rearranged and synthesized as the cells develop. Active synthesis can be noticed during cytokinesis, laying of primary septum, maintenance of lateral cell wall integrity and hyphal tip growth. Chitin synthesis involves coordinated action of two enzymes namely, chitin synthase (that lays new cell wall) and chitinase (that removes the older ones). Since chitin synthase is conserved in different eukaryotic microorganisms that can be a ‘soft target’ for inhibition with small molecules. When chitin synthase is inhibited, it leads to the loss of viability of cells owing to the self- disruption of the cell wall by existing chitinase. Methods: In the described study, small molecules from plant sources were screened for their ability to interfere with hyphal tip growth, by employing Hyphal Tip Burst assay (HTB). Aspergillus niger was used as the model organism. The specific role of these small molecules in interfering with chitin synthesis was established with an in-vitro method. The enzyme required was isolated from Aspergillus niger and its activity was deduced through a novel method involving non-radioactively labelled substrate. The activity of the potential lead molecules were also checked against Candida albicans and Caenorhabditis elegans. The latter was adopted as a surrogate for the pathogenic helminths as it shares similarity with regard to cell wall structure and biochemistry. Moreover, it is widely studied and the methodologies are well established. Results: Out of the 11 compounds and extracts screened, 8 were found to be prospective. They were also found to be effective against Candida albicans and Caenorhabditis elegans. Conclusion: Purified Methyl Ethyl Ketone (MEK) Fraction1 (F1) of Coconut (Cocos nucifera) Shell Extract (COSE) was found to be more effective against Candida albicans with an IC50 value of 3.04 μg/mL and on L4 stage of Caenorhabditis elegans with an IC50 of 77.8 μg/mL.


Phyton ◽  
2019 ◽  
Vol 88 (3) ◽  
pp. 317-324
Author(s):  
Chengjie Shu ◽  
Mengli Zhang ◽  
Weiming Zhang ◽  
Shihong Ma ◽  
Guoqing Chen ◽  
...  

2003 ◽  
Vol 307 (4) ◽  
pp. 928-934 ◽  
Author(s):  
Raymond Y Huang ◽  
Simon J Boulton ◽  
Marc Vidal ◽  
Steve C Almo ◽  
Anne R Bresnick ◽  
...  

PLoS ONE ◽  
2015 ◽  
Vol 10 (11) ◽  
pp. e0142262 ◽  
Author(s):  
Laura Garcia-Segura ◽  
Cei Abreu-Goodger ◽  
Armando Hernandez-Mendoza ◽  
Tzvetanka D. Dimitrova Dinkova ◽  
Luis Padilla-Noriega ◽  
...  

2014 ◽  
Vol 139 ◽  
pp. 33-41 ◽  
Author(s):  
Yiling Lai ◽  
Meichun Xiang ◽  
Shuchun Liu ◽  
Erwei Li ◽  
Yongsheng Che ◽  
...  

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S97-S97
Author(s):  
Amin Haghani ◽  
Hans M Dalton ◽  
Nikoo Safi ◽  
Farimah Shirmohammadi ◽  
Constantinos Sioutas ◽  
...  

Abstract Air pollution (AirPoll) is among the leading human mortality risk factors and yet little is known about the molecular mechanisms of this global environmental toxin. Our recent studies using mouse models even showed genetic variation and sex can alter biological responses to air pollution. To expand genetic studies of AirPoll toxicity throughout the lifespan, we introduced Caenorhabditis elegans as a new AirPoll exposure model which has a short lifespan, high throughput capabilities and shared longevity pathways with mammals. Acute exposure of C. elegans to airborne nanosized AirPoll matter (nPM) caused similar gene expression changes to our prior findings in cell culture and mouse models. Initial C. elegans responses to nPM included antioxidant, inflammatory and Alzheimer homolog genes. The magnitude of changes was dependent on the developmental stage of the worms. Even short term exposure of C. elegans to nPM altered developmental and lifespan hormetic effects, with pathways that included skn-1/Nrf family antioxidant responses. We propose C. elegans as a new and complementary model for mouse and cultured cells to study AirPoll across the lifespan. Future chronic nPM exposure and high throughput genetic screening of C. elegans can identify other major regulators of the developmental and lifespan effects of air pollution. This work was supported by grants R01AG051521 (CEF); R21AG05020 (CEF); Cure Alzheimer’s Fund (CEF); R01GM109028 (SPC), F31AG051382 (HMD) and T32AG000037 (HMD), T32AG052374 (AH).


Sign in / Sign up

Export Citation Format

Share Document