scholarly journals Lycorine Hydrochloride Inhibits the Virulence Traits ofCandida albicans

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Longfei Yang ◽  
Xin Liu ◽  
Yujie Sui ◽  
Zhiming Ma ◽  
Xuechao Feng ◽  
...  
Keyword(s):  
Fungal Pathogen ◽  
Biofilm Formation ◽  
Mammalian Cells ◽  
Inhibitory Concentration ◽  
Antifungal Drugs ◽  
Exopolymeric Substances ◽  
Health Burden ◽  
Ofcandida Albicans ◽  
Opportunistic Fungal Pathogen ◽  
Potential Use

The human opportunistic fungal pathogenCandida albicanscauses a severe health burden while the biofilms formed byC. albicanspresent a kind of infections that are hard to cure, highlighting the pressing need for new antifungal drugs againstC. albicans. This study was to explore the antifungal activities of lycorine hydrochloride (LH) againstC. albicans. The minimal inhibitory concentration (MIC) of LH againstC. albicansSC5314 was 64μM. Below its MIC, LH demonstrated antivirulence property by suppressing adhesion, filamentation, biofilm formation, and development, as well as the production of extracellular phospholipase and exopolymeric substances (EPS). The cytotoxicity of LH against mammalian cells was low, with half maximal inhibitory concentrations (IC50) above 256μM. Moreover, LH showed a synergistic effect with AmB, although its interaction with fluconazole, as well as caspofungin, was indifferent. Thus, our study reports the potential use of LH, alone or in combination with current antifungal drugs, to fightC. albicansinfections.

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

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
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.

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

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.

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

Genes ◽  
2018 ◽  
Vol 9 (11) ◽  
pp. 540 ◽  
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.

scholarly journals Dioscin Inhibits Virulence Factors ofCandida albicans

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Longfei Yang ◽  
Xin Liu ◽  
Lili Zhong ◽  
Yujie Sui ◽  
Guihua Quan ◽  
...  
Keyword(s):  
Virulence Factors ◽  
Biofilm Formation ◽  
Mammalian Cells ◽  
Potential Candidate ◽  
Protective Effects ◽  
Ofcandida Albicans ◽  
Liver And Kidney ◽  
Heavy Burden ◽  
Hepatoprotective Effects ◽  
Low Cytotoxicity

Candida albicansinfections present a heavy burden upon public health, with only a few drugs available, while biofilms formed byC. albicansworsen this situation. Dioscin has antitumor, anti-inflammatory, and hepatoprotective effects, and this study was conducted to evaluate the effects of dioscin on the biofilm formation and development, as well as other virulence factors ofC. albicanssuch as morphological transition, adhesion, and extracellular secreted phospholipase. Our results showed dioscin inhibits these virulence factors and has low cytotoxicity against mammalian cells. Considering protective effects of dioscin against damage on liver and kidney, dioscin may be used as a potential candidate for antifungal development.

scholarly journals Improved Gene Ontology Annotation for Biofilm Formation, Filamentous Growth, and Phenotypic Switching in Candida albicans

2012 ◽  
Vol 12 (1) ◽  
pp. 101-108 ◽  
Author(s):  
Diane O. Inglis ◽  
Marek S. Skrzypek ◽  
Martha B. Arnaud ◽  
Jonathan Binkley ◽  
Prachi Shah ◽  
...  
Keyword(s):  
Gene Ontology ◽  
Candida Albicans ◽  
Gene Product ◽  
Fungal Pathogen ◽  
Biofilm Formation ◽  
Filamentous Growth ◽  
Phenotypic Switching ◽  
Gene Products ◽  
Content Type ◽  
Opportunistic Fungal Pathogen

ABSTRACTThe opportunistic fungal pathogenCandida albicansis a significant medical threat, especially for immunocompromised patients. Experimental research has focused on specific areas ofC. albicansbiology, with the goal of understanding the multiple factors that contribute to its pathogenic potential. Some of these factors include cell adhesion, invasive or filamentous growth, and the formation of drug-resistant biofilms. The Gene Ontology (GO) (www.geneontology.org) is a standardized vocabulary that theCandidaGenome Database (CGD) (www.candidagenome.org) and other groups use to describe the functions of gene products. To improve the breadth and accuracy of pathogenicity-related gene product descriptions and to facilitate the description of as yet uncharacterized but potentially pathogenicity-related genes inCandidaspecies, CGD undertook a three-part project: first, the addition of terms to the biological process branch of the GO to improve the description of fungus-related processes; second, manual recuration of gene product annotations in CGD to use the improved GO vocabulary; and third, computational ortholog-based transfer of GO annotations from experimentally characterized gene products, using these new terms, to uncharacterized orthologs in otherCandidaspecies. Through genome annotation and analysis, we identified candidate pathogenicity genes in seven non-C. albicans Candidaspecies and in one additionalC. albicansstrain, WO-1. We also defined a set ofC. albicansgenes at the intersection of biofilm formation, filamentous growth, pathogenesis, and phenotypic switching of this opportunistic fungal pathogen, which provides a compelling list of candidates for further experimentation.

scholarly journals A Transcriptomics Approach To Unveiling the Mechanisms ofIn VitroEvolution towards Fluconazole Resistance of aCandida glabrataClinical Isolate

2018 ◽  
Vol 63 (1) ◽  
Author(s):  
Mafalda Cavalheiro ◽  
Catarina Costa ◽  
Ana Silva-Dias ◽  
Isabel M. Miranda ◽  
Can Wang ◽  
...  
Keyword(s):  
Fungal Pathogen ◽  
Biofilm Formation ◽  
Molecular Mechanisms ◽  
Antifungal Drugs ◽  
Azole Resistance ◽  
Fluconazole Resistance ◽  
Content Type ◽  
Antifungal Drug Resistance ◽  
Genes Encoding ◽  
Multidrug Resistance Transporters

ABSTRACTCandida glabratais an emerging fungal pathogen. Its increased prevalence is associated with its ability to rapidly develop antifungal drug resistance, particularly to azoles. In order to unravel new molecular mechanisms behind azole resistance, a transcriptomics analysis of the evolution of aC. glabrataclinical isolate (isolate 044) from azole susceptibility to posaconazole resistance (21st day), clotrimazole resistance (31st day), and fluconazole and voriconazole resistance (45th day), induced by longstanding incubation with fluconazole, was carried out. All the evolved strains were found to accumulate lower concentrations of azole drugs than the parental strain, while the ergosterol concentration remained mostly constant. However, only the population displaying resistance to all azoles was found to have a gain-of-function mutation in theC. glabrataPDR1gene, leading to the upregulation of genes encoding multidrug resistance transporters. Intermediate strains, exhibiting posaconazole/clotrimazole resistance and increased fluconazole/voriconazole MIC levels, were found to display alternative ways to resist azole drugs. Particularly, posaconazole/clotrimazole resistance after 31 days was correlated with increased expression of adhesin genes. This finding led us to identify the Epa3 adhesin as a new determinant of azole resistance. Besides being required for biofilm formation, Epa3 expression was found to decrease the intracellular accumulation of azole antifungal drugs. Altogether, this work provides a glimpse of the transcriptomics evolution of aC. glabratapopulation toward multiazole resistance, highlighting the multifactorial nature of the acquisition of azole resistance and pointing out a new player in azole resistance.

Antifungal activity of deferiprone and EDTA against Sporothrix spp.: Effect on planktonic growth and biofilm formation

2020 ◽  
Author(s):  
Raimunda Sâmia Nogueira Brilhante ◽  
Anderson da Cunha Costa ◽  
Vandbergue Santos Pereira ◽  
Mirele Rodrigues Fernandes ◽  
Jonathas Sales de Oliveira ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Biofilm Formation ◽  
Inhibitory Concentration ◽  
Ethylenediaminetetraacetic Acid ◽  
Sporothrix Schenckii ◽  
Sensu Stricto ◽  
Antifungal Drugs ◽  
Synergistic Interaction ◽  
Planktonic Cells ◽  
Yeast Form

Abstract The present study evaluated the antifungal activity of the chelators deferiprone (DFP) and ethylenediaminetetraacetic acid (EDTA) and their effect on biofilm formation of the S. schenckii complex. Eighteen strains of Sporothrix spp. (seven S. brasiliensis, three S. globosa, three S. mexicana and five Sporothrix schenckii sensu stricto) were used. Minimum inhibitory concentration (MIC) values for EDTA and DFP against filamentous forms of Sporothrix spp. ranged from 32 to 128 μg/ml. For antifungal drugs, MIC values ranged from 0.25 to 4 μg/ml for amphotericin B, from 0.25 to 4 μg/ml for itraconazole, and from 0.03 to 0.25 μg/ml for terbinafine. The chelators caused inhibition of Sporothrix spp. in yeast form at concentrations ranging from 16 to 64 μg/ml (for EDTA) and 8 to 32 μg/ml (for DFP). For antifungal drugs, MIC values observed against the yeast varied from 0.03 to 0.5 μg/ml for AMB, 0.03 to 1 μg/ml for ITC, and 0.03 to 0.13 μg/ml for TRB. Both DFP and EDTA presented synergistic interaction with antifungals against Sporothrix spp. in both filamentous and yeast form. Biofilms formed in the presence of the chelators (512 μg/ml) showed a reduction of 47% in biomass and 45% in metabolic activity. Our data reveal that DFP and EDTA reduced the growth of planktonic cells of Sporothrix spp., had synergistic interaction with antifungal drugs against this pathogen, and reduced biofilm formation of Sporothrix spp. Lay Summary Our data reveal that iron chelators deferiprone and ethylenediaminetetraacetic acid reduced the growth of planktonic cells of Sporothrix spp. as well as had synergistic interaction with antifungal drugs against this pathogen and reduced biofilm formation of Sporothrix spp.

scholarly journals The Role of Secretory Pathways in Candida albicans Pathogenesis

2020 ◽  
Vol 6 (1) ◽  
pp. 26 ◽  
Author(s):  
Christiane Rollenhagen ◽  
Sahil Mamtani ◽  
Dakota Ma ◽  
Reva Dixit ◽  
Susan Eszterhas ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Membrane Trafficking ◽  
Fungal Pathogen ◽  
Biofilm Formation ◽  
Secretory Pathways ◽  
Associated Proteins ◽  
Normal Human ◽  
Opportunistic Fungal Pathogen ◽  
Hyphal Formation

Candida albicans is a fungus that is a commensal organism and a member of the normal human microbiota. It has the ability to transition into an opportunistic invasive pathogen. Attributes that support pathogenesis include secretion of virulence-associated proteins, hyphal formation, and biofilm formation. These processes are supported by secretion, as defined in the broad context of membrane trafficking. In this review, we examine the role of secretory pathways in Candida virulence, with a focus on the model opportunistic fungal pathogen, Candida albicans.

scholarly journals A Fluorinated Analogue of Marine Bisindole Alkaloid 2,2-Bis(6-bromo-1H-indol-3-yl)ethanamine as Potential Anti-Biofilm Agent and Antibiotic Adjuvant Against Staphylococcus aureus

2020 ◽  
Vol 13 (9) ◽  
pp. 210
Author(s):  
Raffaella Campana ◽  
Gianmarco Mangiaterra ◽  
Mattia Tiboni ◽  
Emanuela Frangipani ◽  
Francesca Biavasco ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Biofilm Formation ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Inhibitory Concentration ◽  
Fold Reduction ◽  
Bisindole Alkaloid ◽  
Mrsa Strains ◽  
Antibiofilm Agents ◽  
Potential Use

Methicillin resistant Staphylococcus aureus (MRSA) infections represent a major global healthcare problem. Therapeutic options are often limited by the ability of MRSA strains to grow as biofilms on medical devices, where antibiotic persistence and resistance is positively selected, leading to recurrent and chronic implant-associated infections. One strategy to circumvent these problems is the co-administration of adjuvants, which may prolong the efficacy of antibiotic treatments, by broadening their spectrum and lowering the required dosage. The marine bisindole alkaloid 2,2-bis(6-bromo-1H-indol-3-yl)ethanamine (1) and its fluorinated analogue (2) were tested for their potential use as antibiotic adjuvants and antibiofilm agents against S. aureus CH 10850 (MRSA) and S. aureus ATCC 29213 (MSSA). Both compounds showed antimicrobial activity and bisindole 2 enabled 256-fold reduction (ΣFICs = 0.5) in the minimum inhibitory concentration (MIC) of oxacillin for the clinical MRSA strain. In addition, these molecules inhibited biofilm formation of S. aureus strains, and compound 2 showed greater eradicating activity on preformed biofilm compared to 1. None of the tested molecules exerted a viable but non-culturable cells (VBNC) inducing effect at their MIC values. Moreover, both compounds exhibited no hemolytic activity and a good stability in plasma, indicating a non-toxic profile, hence, in particular compound 2, a potential for in vivo applications to restore antibiotic treatment against MRSA infections.

scholarly journals Development of a simple model for studying the effects of antifungal agents on multicellular communities of Aspergillus fumigatus

2007 ◽  
Vol 56 (9) ◽  
pp. 1205-1212 ◽  
Author(s):  
Eilidh Mowat ◽  
John Butcher ◽  
Sue Lang ◽  
Craig Williams ◽  
Gordon Ramage
Keyword(s):  
Aspergillus Fumigatus ◽  
Biofilm Formation ◽  
Antifungal Agents ◽  
Susceptibility Testing ◽  
Growth Conditions ◽  
Antifungal Drugs ◽  
Suitable Model ◽  
Broth Microdilution ◽  
Planktonic Cells ◽  
Opportunistic Fungal Pathogen

Aspergillus fumigatus is an increasingly prevalent opportunistic fungal pathogen of various immunocompromised individuals. It has the ability to form filaments within the lungs, producing dense intertwined mycelial balls, which are difficult to treat. The aim of this study was to develop a suitable model of A. fumigatus to examine the effects of antifungal challenge on these intertwined filamentous communities. A. fumigatus NCPF 7367 growth conditions were optimized on both Thermanox coverslips and on flat-bottomed microtitre plates to establish optimal conidial seeding densities. Isolates were treated with itraconazole, voriconazole, amphotericin B and caspofungin and their overall killing efficiency was measured using an XTT formazan metabolic dye assay. This was compared with the CLSI (formerly NCCLS) methodology of broth microdilution of moulds (standard M38-A). It was shown that 1×105 conidia ml−1 in RPMI 1640 was the optimum concentration of spores for biofilm formation. Filamentous growth characteristics were not observed until 10 h incubation, followed by an exponential increase in the biofilm biomass (hyphae and extracellular material) and cellular activity (metabolism). When susceptibility testing of biofilms was compared with that of planktonic cells by CLSI broth microdilution testing, all antifungal drugs were at least 1000 times less effective at reducing the overall metabolic activity of 90 % of the cells. Overall, this study showed that A. fumigatus has the ability to form coherent multicellular biofilm structures that are resistant to the effects of antifungal drugs.

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