Antifungal effects of alantolactone on Candida albicans: an in vitro study

AbstractThe human fungal pathogen Candida albicans can cause many kinds of infections, including biofilm infections on medical devices, while the available antifungal drugs are limited to only a few. In this study, alantolactone (Ala) demonstrated antifungal activities against C. albicans, as well as other Candida species, with a MIC of 72 μg/mL. Ala could also inhibit the adhesion, yeast-to-hyphal transition, biofilm formation and development of C. albicans. The exopolysaccharide of biofilm matrix and extracellular phospholipase production could also be reduced by Ala treatment. Ala could increase permeability of C. albicans cell membrane and ROS contribute to the antifungal activity of Ala. Overall, the present study suggests that Ala may provide a promising candidate for developing antifungal drugs against C. albicans infections.

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Antifungal Effects of Saponin Extract from Rhizomes of Dioscorea panthaica Prain et Burk against Candida albicans

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2018/6095307 ◽

2018 ◽

Vol 2018 ◽

pp. 1-13 ◽

Cited By ~ 5

Author(s):

Longfei Yang ◽

Xin Liu ◽

Xinming Zhuang ◽

Xuechao Feng ◽

Lili Zhong ◽

...

Keyword(s):

Candida Albicans ◽

Fungal Pathogen ◽

Biofilm Formation ◽

Inhibitory Concentration ◽

Antifungal Drugs ◽

Ros Production ◽

Oxygen Species ◽

Planktonic Cells ◽

Endogenous Reactive Oxygen Species ◽

Antifungal Effects

Candida albicans is the most common fungal pathogen causing serious diseases, while there are only a paucity of antifungal drugs. Therefore, the present study was performed to investigate the antifungal effects of saponin extract from rhizomes of Dioscorea panthaica Prain et Burk (Huangshanyao Saponin extract, HSE) against C. albicans. HSE inhibits the planktonic growth and biofilm formation and development of C. albicans. 16–64 μg/mL of HSE could inhibit adhesion to polystyrene surfaces, transition from yeast to filamentous growth, and production of secreted phospholipase and could also induce endogenous reactive oxygen species (ROS) production and disrupt cell membrane in planktonic cells. Inhibitory activities against extracellular exopolysaccharide (EPS) production and ROS production in preformed biofilms could be inhibited by 64–256 μg/mL of HSE. Cytotoxicity against human Chang’s liver cells is low, with a half maximal inhibitory concentration (IC50) of about 256 μg/mL. In sum, our study suggested that HSE might be used as a potential antifungal therapeutic against C. albicans.

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Nanostructured Selenium for Preventing Biofilm Formation on Medical Devices

MRS Proceedings ◽

10.1557/opl.2012.44 ◽

2012 ◽

Vol 1415 ◽

Author(s):

Qi Wang ◽

Thomas J. Webster

Keyword(s):

Staphylococcus Aureus ◽

Medical Device ◽

Medical Devices ◽

Biofilm Formation ◽

In Vitro Study ◽

Common Cause ◽

Persistent Infections ◽

Wide Range ◽

Novel Material

ABSTRACTBiofilms are a common cause of persistent infections on medical devices as they are easy to form and hard to treat. Selenium and its compounds are considered to be a novel material for a wide range of applications including anticancer applications and antibacterial applications. The objective of this study was to coat selenium nanoparticles on the surface of polycarbonate medical devices and examine their effectiveness at preventing biofilm formation. The results of this in vitro study showed that the selenium coating significantly inhibited Staphylococcus aureus growth on the surface of polycarbonate after 24 hours. Thus, this study suggests that coating polymers with nanostructured selenium is a fast and effective way to reduce bacteria functions leading to medical device infections.

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Simple Carbohydrate Derivatives Diminish the Formation of Biofilm of the Pathogenic Yeast Candida albicans

Antibiotics ◽

10.3390/antibiotics9010010 ◽

2019 ◽

Vol 9 (1) ◽

pp. 10 ◽

Cited By ~ 1

Author(s):

Olena P. Ishchuk ◽

Olov Sterner ◽

Ulf Ellervik ◽

Sophie Manner

Keyword(s):

Candida Albicans ◽

Fungal Pathogen ◽

Biofilm Formation ◽

Untreated Control ◽

Morphological Transition ◽

Pathogenic Yeast ◽

Yeast Form ◽

Human Fungal Pathogen ◽

Morphological Transitions ◽

Simple Carbohydrate

The opportunistic human fungal pathogen Candida albicans relies on cell morphological transitions to develop biofilm and invade the host. In the current study, we developed new regulatory molecules, which inhibit the morphological transition of C. albicans from yeast-form cells to cells forming hyphae. These compounds, benzyl α-l-fucopyranoside and benzyl β-d-xylopyranoside, inhibit the hyphae formation and adhesion of C. albicans to a polystyrene surface, resulting in a reduced biofilm formation. The addition of cAMP to cells treated with α-l-fucopyranoside restored the yeast-hyphae switch and the biofilm level to that of the untreated control. In the β-d-xylopyranoside treated cells, the biofilm level was only partially restored by the addition of cAMP, and these cells remained mainly as yeast-form cells.

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Tolerance to fluconazole in Candida albicans is regulated by temperature and aneuploidy

Access Microbiology ◽

10.1099/acmi.cc2021.po0106 ◽

2021 ◽

Vol 3 (12) ◽

Author(s):

FENG YANG ◽

YUANYING JIANG ◽

JUDITH BERMAN

Keyword(s):

Candida Albicans ◽

High Temperature ◽

Fungal Pathogen ◽

Drug Tolerance ◽

Antifungal Drugs ◽

Clinical Isolates ◽

Human Fungal Pathogen ◽

Genes Encoding ◽

Aneuploid Chromosome ◽

Definition Of

Candida albicans is a prevalent human fungal pathogen. Azoles are the most widely used antifungal drugs. Drug tolerance in bacteria is well defined and thoroughly studied, but in fungi, the definition of drug tolerance and the mechanism that drive it are not well understood. Here, we found that a large proportion of clinical isolates were intrinsically tolerant to fluconazole, and/or could be induced by high temperature (37°C) to become tolerant (conditionally tolerant). When treated with inhibitory doses of fluconazole, non-tolerant strains became tolerant by forming aneuploids involving different chromosomes, with chromosome R duplication as the most recurrent mechanism. Tolerance determines the ability to grow in the presence of fluconazole and other azoles, in a manner independent of the MIC. Both temperature conditional tolerance and the associated aneuploidy were sensitive to FK506, an inhibitor of calcineurin. Intrinsic and conditional tolerance were also abolished by deletions of genes encoding the calcineurin (CMP1 and CNB1). However, the dependence of tolerance on calcineurin could be bypassed by a different aneuploid chromosome. Thus, fluconazole tolerance in C. albicans is regulated by temperature and by aneuploidy and is dependent upon aneuploidy, but this dependence can be bypassed by an additional aneuploidy.

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Carnitine-Dependent Transport of Acetyl Coenzyme A in Candida albicans Is Essential for Growth on Nonfermentable Carbon Sources and Contributes to Biofilm Formation

Eukaryotic Cell ◽

10.1128/ec.00017-08 ◽

2008 ◽

Vol 7 (4) ◽

pp. 610-618 ◽

Cited By ~ 32

Author(s):

Karin Strijbis ◽

Carlo W. T. van Roermund ◽

Wouter F. Visser ◽

Els C. Mol ◽

Janny van den Burg ◽

...

Keyword(s):

Candida Albicans ◽

Fatty Acid ◽

Fungal Pathogen ◽

Biofilm Formation ◽

Carbon Sources ◽

Acetyl Coa ◽

Oxidation Activity ◽

Acetyl Coenzyme A ◽

Human Fungal Pathogen ◽

Peroxisomal Fatty Acid

ABSTRACT In eukaryotes, acetyl coenzyme A (acetyl-CoA) produced during peroxisomal fatty acid β-oxidation needs to be transported to mitochondria for further metabolism. Two parallel pathways for acetyl-CoA transport have been identified in Saccharomyces cerevisiae; one is dependent on peroxisomal citrate synthase (Cit), while the other requires peroxisomal and mitochondrial carnitine acetyltransferase (Cat) activities. Here we show that the human fungal pathogen Candida albicans lacks peroxisomal Cit, relying exclusively on Cat activity for transport of acetyl units. Deletion of the CAT2 gene encoding the major Cat enzyme in C. albicans resulted in a strain that had lost both peroxisomal and mitochondrion-associated Cat activities, could not grow on fatty acids or C2 carbon sources (acetate or ethanol), accumulated intracellular acetyl-CoA, and showed greatly reduced fatty acid β-oxidation activity. The cat2 null mutant was, however, not attenuated in virulence in a mouse model of systemic candidiasis. These observations support our previous results showing that peroxisomal fatty acid β-oxidation activity is not essential for C. albicans virulence. Biofilm formation by the cat2 mutant on glucose was slightly reduced compared to that by the wild type, although both strains grew at the same rate on this carbon source. Our data show that C. albicans has diverged considerably from S. cerevisiae with respect to the mechanism of intracellular acetyl-CoA transport and imply that carnitine dependence may be an important trait of this human fungal pathogen.

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The SUMO protease Ulp2 regulates genome stability and drug resistance in the human fungal pathogen Candida albicans

10.1101/2021.12.06.471441 ◽

2021 ◽

Author(s):

Marzia Rizzo ◽

Natthapon Soisangwan ◽

Jan Soetaert ◽

Samuel Vega-Estevez ◽

Anna Selmecki ◽

...

Keyword(s):

Drug Resistance ◽

Candida Albicans ◽

Fungal Pathogen ◽

Genome Instability ◽

Antifungal Drugs ◽

Antifungal Drug ◽

Genome Plasticity ◽

Sumo Protease ◽

Human Fungal Pathogen ◽

Life Threatening

AbstractStress-induced genome instability in microbial organisms is emerging as a critical regulatory mechanism for driving rapid and reversible adaption to drastic environmental changes. In Candida albicans, a human fungal pathogen that causes life-threatening infections, genome plasticity confers increased virulence and antifungal drug resistance. Discovering the mechanisms regulating C. albicans genome plasticity is a priority to understand how this and other microbial pathogens establish life-threatening infections and develop resistance to antifungal drugs. We identified the SUMO protease Ulp2 as a critical regulator of C. albicans genome integrity through genetic screening. Deletion of ULP2 leads to hypersensitivity to genotoxic agents and increased genome instability. This increased genome diversity causes reduced fitness under standard laboratory growth conditions but enhances adaptation to stress, making ulp2Δ/Δ cells more likely to thrive in the presence of antifungal drugs. Whole-genome sequencing indicates that ulp2Δ/Δ cells counteract antifungal drug-induced stress by developing segmental aneuploidies of chromosome R and chromosome I. We demonstrate that intrachromosomal repetitive elements drive the formation of complex novel genotypes with adaptive power.

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Simple Carbohydrate Derivatives Diminish the Formation of Biofilm of Candida albicans

10.21203/rs.2.16042/v2 ◽

2019 ◽

Author(s):

Olena P. Ishchuk ◽

Olov Sterner ◽

Ulf Ellervik ◽

Sophie Manner

Keyword(s):

Candida Albicans ◽

Fungal Pathogen ◽

Biofilm Formation ◽

Untreated Control ◽

Morphological Transition ◽

Yeast Form ◽

Polystyrene Surface ◽

Human Fungal Pathogen ◽

Morphological Transitions ◽

Simple Carbohydrate

Abstract The opportunistic human fungal pathogen Candida albicans rely on cell morphological transitions to develop biofilm and invade the host. In the current study, we developed new regulatory molecules, which inhibit the morphological transition of C. albicans from yeast-form cells to cells forming hyphae. These compounds, benzyl α-L-fucopyranoside and benzyl β-D-xylopyranoside, inhibit the morphological switching and adhesion of C. albicans to a polystyrene surface, resulting in a reduced biofilm formation. The addition of cAMP to cells treated with α-L-fucopyranoside restored the yeast-hyphae switch and the biofilm level to that of the untreated control. In the β-D-xylopyranoside treated cells, the biofilm level was only partially restored by the addition of cAMP, and these cells remained mainly as yeast-form cells.

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Ploidy determines the consequences of antifungal-induced mutagenesis in Candida albicans, a human fungal pathogen

10.1101/686881 ◽

2019 ◽

Cited By ~ 1

Author(s):

Ognenka Avramovska ◽

Meleah A. Hickman

Keyword(s):

Cell Wall ◽

Candida Albicans ◽

Environmental Stress ◽

Genome Size ◽

Fungal Pathogen ◽

Fungal Pathogens ◽

Antifungal Drugs ◽

Relevant Model ◽

Human Fungal Pathogen ◽

Induced Mutagenesis

AbstractOrganismal ploidy state and environmental stress impact the mutational spectrum and the mutational rate. The human fungal pathogen Candida albicans, serves as a clinically relevant model for studying the interaction between eukaryotic ploidy and stress-induced mutagenesis. In this study, we compared the rates and types of genome perturbations in diploid and tetraploid C. albicans following exposure to two classes of antifungal drugs, azoles and echinocandins. We measured mutations at three different scales: point mutation, loss-of-heterozygosity (LOH), and genome size changes in cells treated with fluconazole and caspofungin. We find that caspofungin induced higher rates of mutation than fluconazole, likely an indirect result from the stress associated with cell wall perturbations rather than an inherent genotoxicity. Furthermore, we found disproportionately elevated rates of LOH and genome size changes in response to both antifungals in tetraploid C. albicans compared to diploid C. albicans, suggesting that the magnitude of stress-induced mutagenesis results from an interaction between ploidy state and the environment. These results have both clinical and evolutionary implications for how fungal pathogens generate mutations in response to antifungal drug stress, and may facilitate the emergence of antifungal resistance.

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Chromosome 1 trisomy overcomes the block of sphingolipid biosynthesis caused by aureobasidin A and confers pleiotropic effects on susceptibility to antifungals in Candida albicans

10.1101/2020.04.07.031112 ◽

2020 ◽

Author(s):

Yi Xu ◽

Feng Yang

Keyword(s):

Candida Albicans ◽

Fungal Pathogen ◽

Membrane Lipid ◽

Antifungal Drugs ◽

Pleiotropic Effects ◽

Chromosome 1 ◽

Eukaryotic Cells ◽

Human Fungal Pathogen ◽

Aureobasidin A ◽

Sphingolipid Biosynthesis

AbstractSphingolipids are important membrane lipid components of eukaryotic cells. In Candida albicans, chromosome 1 trisomy not only overcame the block of sphingolipid biosynthesis caused by aureobasidin A, but also altered tolerance to three of the four major classes of antifungal drugs. Two haploinsufficient genes on chromosome 1, PDR16 and IPT1, were associated with tolerance to aureobasidin A. This study illustrates an example of multi-drug tolerance caused by aneuploidy in the human fungal pathogen C. albicans.

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Transcriptomic and Genomic Approaches for Unravelling Candida albicans Biofilm Formation and Drug Resistance—An Update

Genes ◽

10.3390/genes9110540 ◽

2018 ◽

Vol 9 (11) ◽

pp. 540 ◽

Cited By ~ 6

Author(s):

Pei Chong ◽

Voon Chin ◽

Won Wong ◽

Priya Madhavan ◽

Voon Yong ◽

...

Keyword(s):

Drug Resistance ◽

Candida Albicans ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Fungal Pathogen ◽

Biofilm Formation ◽

Antifungal Drugs ◽

Yeast Cells ◽

Whole Genome ◽

Different Strains

Candida albicans is an opportunistic fungal pathogen, which causes a plethora of superficial, as well as invasive, infections in humans. The ability of this fungus in switching from commensalism to active infection is attributed to its many virulence traits. Biofilm formation is a key process, which allows the fungus to adhere to and proliferate on medically implanted devices as well as host tissue and cause serious life-threatening infections. Biofilms are complex communities of filamentous and yeast cells surrounded by an extracellular matrix that confers an enhanced degree of resistance to antifungal drugs. Moreover, the extensive plasticity of the C. albicans genome has given this versatile fungus the added advantage of microevolution and adaptation to thrive within the unique environmental niches within the host. To combat these challenges in dealing with C. albicans infections, it is imperative that we target specifically the molecular pathways involved in biofilm formation as well as drug resistance. With the advent of the -omics era and whole genome sequencing platforms, novel pathways and genes involved in the pathogenesis of the fungus have been unraveled. Researchers have used a myriad of strategies including transcriptome analysis for C. albicans cells grown in different environments, whole genome sequencing of different strains, functional genomics approaches to identify critical regulatory genes, as well as comparative genomics analysis between C. albicans and its closely related, much less virulent relative, C. dubliniensis, in the quest to increase our understanding of the mechanisms underlying the success of C. albicans as a major fungal pathogen. This review attempts to summarize the most recent advancements in the field of biofilm and antifungal resistance research and offers suggestions for future directions in therapeutics development.

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