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.

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 The GPI-modified proteins Pga59 and Pga62 of Candida albicans are required for cell wall integrity

Microbiology ◽  
2009 ◽  
Vol 155 (6) ◽  
pp. 2004-2020 ◽  
Author(s):  
Emilia Moreno-Ruiz ◽  
Giuseppe Ortu ◽  
Piet W. J. de Groot ◽  
Fabien Cottier ◽  
Céline Loussert ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Fungal Pathogens ◽  
High Sensitivity ◽  
Wall Structure ◽  
Minor Role ◽  
Cell Wall Proteins ◽  
Calcofluor White ◽  
Fungal Cell ◽  
A Minor

The fungal cell wall is essential in maintaining cellular integrity and plays key roles in the interplay between fungal pathogens and their hosts. The PGA59 and PGA62 genes encode two short and related glycosylphosphatidylinositol-anchored cell wall proteins and their expression has been previously shown to be strongly upregulated when the human pathogen Candida albicans grows as biofilms. Using GFP fusion proteins, we have shown that Pga59 and Pga62 are cell-wall-located, N- and O-glycosylated proteins. The characterization of C. albicans pga59Δ/pga59Δ, pga62Δ/pga62Δ and pga59Δ/pga59Δ pga62Δ/pga62Δ mutants suggested a minor role of these two proteins in hyphal morphogenesis and that they are not critical to biofilm formation. Importantly, the sensitivity to different cell-wall-perturbing agents was altered in these mutants. In particular, simultaneous inactivation of PGA59 and PGA62 resulted in high sensitivity to Calcofluor white, Congo red and nikkomicin Z and in resistance to caspofungin. Furthermore, cell wall composition and observation by transmission electron microscopy indicated an altered cell wall structure in the mutant strains. Collectively, these data suggest that the cell wall proteins Pga59 and Pga62 contribute to cell wall stability and structure.

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 Spatial Distribution of a Porphyrin-Based Photosensitizer Reveals Mechanism of Photodynamic Inactivation of Candida albicans

2021 ◽  
Vol 8 ◽  
Author(s):  
Thomas Voit ◽  
Fabian Cieplik ◽  
Johannes Regensburger ◽  
Karl-Anton Hiller ◽  
Anita Gollmer ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Fungal Infections ◽  
Cell Envelope ◽  
Antimicrobial Photodynamic Therapy ◽  
Fungal Cell ◽  
Before And After ◽  
Antifungal Action ◽  
Complete Cell ◽  
Further Development

The antimicrobial photodynamic therapy (aPDT) is a promising approach for the control of microbial and especially fungal infections such as mucosal mycosis. TMPyP [5,10,15, 20-tetrakis(1-methylpyridinium-4-yl)-porphyrin tetra p-toluenesulfonate] is an effective photosensitizer (PS) that is commonly used in aPDT. The aim of this study was to examine the localization of TMPyP in Candida albicans before and after irradiation with visible light to get information about the cellular mechanism of antifungal action of the photodynamic process using this PS. Immediately after incubation of C. albicans with TMPyP, fluorescence microscopy revealed an accumulation of the PS in the cell envelope. After irradiation with blue light the complete cell showed red fluorescence, which indicates, that aPDT is leading to a damage in the cell wall with following influx of PS into the cytosol. Incubation of C. albicans with Wheat Germ Agglutinin (WGA) could confirm the cell wall as primary binding site of TMPyP. The finding that the porphyrin accumulates in the fungal cell wall and does not enter the interior of the cell before irradiation makes it unlikely that resistances can emerge upon aPDT. The results of this study may help in further development and modification of PS in order to increase efficacy against fungal infections such as those caused by C. albicans.

scholarly journals Virulence Factor and Pathogenicity of Candida albicans in Oral Candidiasis

2013 ◽  
Vol 4 (4) ◽  
pp. 267-271 ◽  
Author(s):  
Abdillah Imron Nasution
Keyword(s):  
Antibiotic Resistance ◽  
Candida Albicans ◽  
Immune System ◽  
Virulence Factors ◽  
Virulence Factor ◽  
Oral Candidiasis ◽  
Complex Process ◽  
Phenotype Switching

ABSTRACT Candida albicans is an opportunistic fungus causing various forms of candidiasis. However, under certain circumstances it is capable of becoming pathogenic. Pathogenicity of oral candidiasis is a complex process and there is no one factor that can be regarded as the direct cause. This review aims to explain the virulence factors of Candida albicans in oral candidiasis infection and its relation to homeostasis in the mouth. Virulence factors of Candida albicans which is closely related to the nature of pathogens include: adherence and coaggregation, interference of immune system, phenotype switching and several supporting factors such as antibiotic resistance and immunomodulating. How to cite this article Nasution AI. Virulence Factor and Pathogenicity of Candida albicans in Oral Candidiasis. World J Dent 2013;4(4):267-271.

scholarly journals Candida albicans Sun41p, a Putative Glycosidase, Is Involved in Morphogenesis, Cell Wall Biogenesis, and Biofilm Formation

2007 ◽  
Vol 6 (11) ◽  
pp. 2056-2065 ◽  
Author(s):  
Ekkehard Hiller ◽  
Sonja Heine ◽  
Herwig Brunner ◽  
Steffen Rupp
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Biofilm Formation ◽  
Cell Monolayer ◽  
The Sun ◽  
Calcofluor White ◽  
Cellular Processes ◽  
Cell Wall Biogenesis ◽  
Reduced Adherence ◽  
Higher Sensitivity

ABSTRACT The SUN gene family has been defined in Saccharomyces cerevisiae and comprises a fungus-specific family of proteins which show high similarity in their C-terminal domains. Genes of this family are involved in different cellular processes, like DNA replication, aging, mitochondrial biogenesis, and cytokinesis. In Candida albicans the SUN family comprises two genes, SUN41 and SIM1. We demonstrate that C. albicans mutants lacking SUN41 show similar defects as found for S. cerevisiae, including defects in cytokinesis. In addition, the SUN41 mutant showed a higher sensitivity towards the cell wall-disturbing agent Congo red, whereas no difference was observed in the presence of calcofluor white. Compared to the wild type, SUN41 deletion strains exhibited a defect in biofilm formation, a reduced adherence on a Caco-2 cell monolayer, and were unable to form hyphae on solid medium under the conditions tested. Interestingly, Sun41p was found to be secreted in the medium of cells growing as blastospores as well as those forming hyphae. Our results support a function of SUN41p as a glycosidase involved in cytokinesis, cell wall biogenesis, adhesion to host tissue, and biofilm formation, indicating an important role in the host-pathogen interaction.

Sign in / Sign up

Export Citation Format

Share Document