Simple Carbohydrate Derivatives Diminish the Formation of Biofilm of Candida albicans

10.21203/rs.2.16042/v1 ◽

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.

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.

In Fungal Intracellular Pathogenesis, Form Determines Fate

mBio ◽

10.1128/mbio.02092-18 ◽

2018 ◽

Vol 9 (5) ◽

Cited By ~ 4

Author(s):

Robin C. May ◽

Arturo Casadevall

Keyword(s):

Candida Albicans ◽

Fungal Pathogen ◽

Membrane Integrity ◽

Pathogenic Fungi ◽

Morphological Transition ◽

Physical Damage ◽

Fungal Cell ◽

Morphological Transitions ◽

Pathogenic Microbes ◽

Phagosomal Membrane

ABSTRACT For pathogenic microbes to survive ingestion by macrophages, they must subvert powerful microbicidal mechanisms within the phagolysosome. After ingestion, Candida albicans undergoes a morphological transition producing hyphae, while the surrounding phagosome exhibits a loss of phagosomal acidity. However, how these two events are related has remained enigmatic. Now Westman et al. (mBio 9:e01226-18, 2018, https://doi.org/10.1128/mBio.01226-18) report that phagosomal neutralization results from disruption of phagosomal membrane integrity by the enlarging hyphae, directly implicating the morphological transition in physical damage that promotes intracellular survival. The C. albicans intracellular strategy shows parallels with another fungal pathogen, Cryptococcus neoformans, where a morphological changed involving capsular enlargement intracellularly is associated with loss of membrane integrity and death of the host cell. These similarities among distantly related pathogenic fungi suggest that morphological transitions that are common in fungi directly affect the outcome of the fungal cell-macrophage interaction. For this class of organisms, form determines fate in the intracellular environment.

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

10.1101/2021.01.25.428193 ◽

2021 ◽

Author(s):

Xin Liu ◽

Lili Zhong ◽

Zhiming Ma ◽

Yujie Sui ◽

Jia’nan Xie ◽

...

Keyword(s):

Candida Albicans ◽

Medical Devices ◽

Fungal Pathogen ◽

Biofilm Formation ◽

In Vitro Study ◽

Antifungal Drugs ◽

Promising Candidate ◽

Human Fungal Pathogen ◽

Antifungal Effects

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.

Induction of theCandida albicansFilamentous Growth Program by Relief of Transcriptional Repression: A Genome-wide Analysis

Molecular Biology of the Cell ◽

10.1091/mbc.e05-01-0073 ◽

2005 ◽

Vol 16 (6) ◽

pp. 2903-2912 ◽

Cited By ~ 207

Author(s):

David Kadosh ◽

Alexander D. Johnson

Keyword(s):

Candida Albicans ◽

Transcriptional Repression ◽

Fungal Pathogen ◽

Morphological Transition ◽

Whole Genome ◽

Transcriptional Repressors ◽

Genome Wide Analysis ◽

Human Fungal Pathogen ◽

Genome Wide ◽

A Genome

Candida albicans, the major human fungal pathogen, undergoes a reversible morphological transition from blastospores (round budding cells) to filaments (elongated cells attached end-to-end). This transition, which is induced upon exposure of C. albicans cells to a number of host conditions, including serum and body temperature (37°C), is required for virulence. Using whole-genome DNA microarray analysis, we describe 61 genes that are significantly induced (≥2-fold) during the blastospore to filament transition that takes place in response to exposure to serum and 37°C. We next show that approximately half of these genes are transcriptionally repressed in the blastospore state by three transcriptional repressors, Rfg1, Nrg1, and Tup1. We conclude that the relief of this transcriptional repression plays a key role in bringing the C. albicans filamentous growth program into play, and we describe the framework of this transcriptional circuit.

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.

Recent advances in understanding Candida albicans hyphal growth

F1000Research ◽

10.12688/f1000research.18546.1 ◽

2019 ◽

Vol 8 ◽

pp. 700 ◽

Cited By ~ 2

Author(s):

Robert A. Arkowitz ◽

Martine Bassilana

Keyword(s):

Candida Albicans ◽

Medical Research ◽

Filamentous Fungi ◽

Fungal Pathogen ◽

Fungal Pathogens ◽

Morphological Changes ◽

Hyphal Growth ◽

Yeast Form ◽

Intensive Research ◽

Human Fungal Pathogen

Morphological changes are critical for the virulence of a range of plant and human fungal pathogens. Candida albicans is a major human fungal pathogen whose ability to switch between different morphological states is associated with its adaptability and pathogenicity. In particular, C. albicans can switch from an oval yeast form to a filamentous hyphal form, which is characteristic of filamentous fungi. What mechanisms underlie hyphal growth and how are they affected by environmental stimuli from the host or resident microbiota? These questions are the focus of intensive research, as understanding C. albicans hyphal growth has broad implications for cell biological and medical research.

A Re-Evaluation of the Relationship between Morphology and Pathogenicity in Candida Species

Journal of Fungi ◽

10.3390/jof6010013 ◽

2020 ◽

Vol 6 (1) ◽

pp. 13

Author(s):

David Kadosh ◽

Vasanthakrishna Mundodi

Keyword(s):

Candida Albicans ◽

Candida Species ◽

Fungal Pathogen ◽

Future Research ◽

Morphological Transition ◽

Definitive Evidence ◽

Human Fungal Pathogen ◽

The Relationship ◽

Lines Of Evidence

Many pathogenic Candida species possess the ability to undergo a reversible morphological transition from yeast to filamentous cells. In Candida albicans, the most frequently isolated human fungal pathogen, multiple lines of evidence strongly suggest that this transition is associated with virulence and pathogenicity. While it has generally been assumed that non-albicans Candida species (NACS) are less pathogenic than C. albicans, in part, because they do not filament as well, definitive evidence is lacking. Interestingly, however, a recent study suggests that filamentation of NACS is associated with reduced, rather than increased, pathogenicity. These findings, in turn, challenge conventional views and suggest that there are fundamental evolutionary differences in the morphology–pathogenicity relationship in C. albicans vs. NACS. The findings also raise many new and intriguing questions and open new avenues for future research, which are discussed.

pH-Dependant Antifungal Activity of Valproic Acid against the Human Fungal Pathogen Candida albicans

Frontiers in Microbiology ◽

10.3389/fmicb.2017.01956 ◽

2017 ◽

Vol 8 ◽

Cited By ~ 9

Author(s):

Julien Chaillot ◽

Faiza Tebbji ◽

Carlos García ◽

Hugo Wurtele ◽

René Pelletier ◽

...

Keyword(s):

Valproic Acid ◽

Candida Albicans ◽

Antifungal Activity ◽

Fungal Pathogen ◽

Human Fungal Pathogen

An improved transformation protocol for the human fungal pathogen Candida albicans

Current Genetics ◽

10.1007/s00294-002-0349-0 ◽

2003 ◽

Vol 42 (6) ◽

pp. 339-343 ◽

Cited By ~ 143

Author(s):

Andrea Walther ◽

Jürgen Wendland

Keyword(s):

Candida Albicans ◽

Fungal Pathogen ◽

Transformation Protocol ◽

Human Fungal Pathogen