scholarly journals Bioactive Coatings with Ag-Camphorimine Complexes to Prevent Surface Colonization by the Pathogenic Yeast Candida albicans

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 638
Author(s):  
M. Joana F. Pinheiro ◽  
Joana P. Costa ◽  
Fernanda Marques ◽  
Nuno P. Mira ◽  
M. Fernanda N. N. Carvalho ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Medical Devices ◽  
Mammalian Cells ◽  
Surface Engineering ◽  
Pathogenic Yeast ◽  
Bioactive Coatings ◽  
Clinical Strains ◽  
Persistent Infections ◽  
Compound Q ◽  
Significant Step

Currently there is a gap between the rate of new antifungal development and the emergence of resistance among Candida clinical strains, particularly threatened by the extreme adhesiveness of C. albicans to indwelling medical devices. Two silver camphorimine complexes, [Ag(OH){OC10H14N(C6H4)2NC10H14O}] (compound P) and [{Ag(OC10H14NC6H4CH3-p)}2(μ-O)] (compound Q), are herein demonstrated as having high inhibiting activity towards the growth of Candida albicans and Candida glabrata clinical strains resistant to azoles, the frontline antifungals used in clinical practice. Compounds P and Q were also explored as bioactive coatings to prevent colonization by C. albicans and colonize the surface of indwelling medical devices, resulting in persistent infections. Functionalization of stainless steel with polycaprolactone (PCL) matrix embedded with compounds P or Q was reported for the first time to inhibit the colonization of C. albicans by 82% and 75%, respectively. The coating of PCL loaded with Q or P did not cause cytotoxic effects in mammalian cells, demonstrating the biocompatibility of the explored approach. The identification and further exploration of new approaches for surface engineering based on new molecules that can sensitize resistant strains, as herein demonstrated for complexes P and Q, is a significant step forward to improve the successful treatment of candidiasis.

scholarly journals Inhibitors of cellular signalling are cytotoxic or block the budded-to-hyphal transition in the pathogenic yeast Candida albicans

2009 ◽  
Vol 58 (6) ◽  
pp. 779-790 ◽  
Author(s):  
Kurt A. Toenjes ◽  
Benjamin C. Stark ◽  
Krista M. Brooks ◽  
Douglas I. Johnson
Keyword(s):  
Candida Albicans ◽  
Cell Biology ◽  
Mammalian Cells ◽  
Signalling Pathways ◽  
Pathogenic Yeast ◽  
Fungal Host ◽  
Cellular Processes ◽  
Localization Analysis ◽  
Inhibitory Molecules ◽  
G Protein Coupled

The pathogenic yeast Candida albicans can grow in multiple morphological states including budded, pseudohyphal and true hyphal forms. The ability to interconvert between budded and hyphal forms, herein termed the budded-to-hyphal transition (BHT), is important for C. albicans virulence, and is regulated by multiple environmental and cellular signals. To identify small-molecule inhibitors of known cellular processes that can also block the BHT, a microplate-based morphological assay was used to screen the BIOMOL–Institute of Chemistry and Cell Biology (ICCB) Known Bioactives collection from the ICCB-Longwood Screening Facility (Harvard Medical School, Boston, MA, USA). Of 480 molecules tested, 53 were cytotoxic to C. albicans and 16 were able to block the BHT without inhibiting budded growth. These 16 BHT inhibitors affected protein kinases, protein phosphatases, Ras signalling pathways, G protein-coupled receptors, calcium homeostasis, nitric oxide and guanylate cyclase signalling, and apoptosis in mammalian cells. Several of these molecules were also able to inhibit filamentous growth in other Candida species, as well as the pathogenic filamentous fungus Aspergillus fumigatus, suggesting a broad fungal host range for these inhibitory molecules. Results from secondary assays, including hyphal-specific transcription and septin localization analysis, were consistent with the inhibitors affecting known BHT signalling pathways in C. albicans. Therefore, these molecules will not only be invaluable in deciphering the signalling pathways regulating the BHT, but also may serve as starting points for potential new antifungal therapeutics.

Antifungal Activity Directed Toward the Cell Wall by 2-Cyclohexylidenhydrazo- 4-Phenyl-Thiazole Against Candida albicans

2019 ◽  
Vol 19 (4) ◽  
pp. 428-438 ◽  
Author(s):  
Nívea P. de Sá ◽  
Ana P. Pôssa ◽  
Pilar Perez ◽  
Jaqueline M.S. Ferreira ◽  
Nayara C. Fonseca ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Antifungal Activity ◽  
Mammalian Cells ◽  
C Elegans ◽  
Buccal Epithelial Cells ◽  
Mutant Strains ◽  
Low Toxicity ◽  
High Concentrations ◽  
Mic Value

<p>Background: The increasing incidence of invasive forms of candidiasis and resistance to antifungal therapy leads us to seek new and more effective antifungal compounds. </P><P> Objective: To investigate the antifungal activity and toxicity as well as to evaluate the potential targets of 2- cyclohexylidenhydrazo-4-phenyl-thiazole (CPT) in Candida albicans. </P><P> Methods: The antifungal activity of CPT against the survival of C. albicans was investigated in Caenorhabditis elegans. Additionally, we determined the effect of CPT on the inhibition of C. albicans adhesion capacity to buccal epithelial cells (BECs), the toxicity of CPT in mammalian cells, and the potential targets of CPT in C. albicans. </P><P> Results: CPT exhibited a minimum inhibitory concentration (MIC) value of 0.4-1.9 µg/mL. Furthermore, CPT at high concentrations (>60 x MIC) showed no or low toxicity in HepG2 cells and <1% haemolysis in human erythrocytes. In addition, CPT decreased the adhesion capacity of yeasts to the BECs and prolonged the survival of C. elegans infected with C. albicans. Analysis of CPT-treated cells showed that their cell wall was thinner than that of untreated cells, especially the glucan layer. We found that there was a significantly lower quantity of 1,3-β-D-glucan present in CPT-treated cells than that in untreated cells. Assays performed on several mutant strains showed that the MIC value of CPT was high for its antifungal activity on yeasts with defective 1,3-β-glucan synthase. </P><P> Conclusion: In conclusion, CPT appears to target the cell wall of C. albicans, exhibits low toxicity in mammalian cells, and prolongs the survival of C. elegans infected with C. albicans.</p>

scholarly journals The Inflammatory Response Induced by Aspartic Proteases of Candida albicans Is Independent of Proteolytic Activity

2010 ◽  
Vol 78 (11) ◽  
pp. 4754-4762 ◽  
Author(s):  
Donatella Pietrella ◽  
Anna Rachini ◽  
Neelam Pandey ◽  
Lydia Schild ◽  
Mihai Netea ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Inflammatory Response ◽  
Proteolytic Activity ◽  
Necrosis Factor Alpha ◽  
Pathogenic Yeast ◽  
Aspartic Proteases ◽  
Akt Activation ◽  
Tnf Α ◽  
Factor Alpha ◽  
Pepstatin A

ABSTRACT The secretion of aspartic proteases (Saps) has long been recognized as a virulence-associated trait of the pathogenic yeast Candida albicans. In this study, we report that different recombinant Saps, including Sap1, Sap2, Sap3, and Sap6, have differing abilities to induce secretion of proinflammatory cytokines by human monocytes. In particular Sap1, Sap2, and Sap6 significantly induced interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-α), and IL-6 production. Sap3 was able to stimulate the secretion of IL-1β and TNF-α. All Saps tested were able to induce Ca2+ influx in monocytes. Treatment of these Saps with pepstatin A did not have any effect on cytokine secretion, indicating that their stimulatory potential was independent from their proteolytic activity. The capacity of Saps to induce inflammatory cytokine production was also independent from protease-activated receptor (PAR) activation and from the optimal pH for individual Sap activity. The interaction of Saps with monocytes induced Akt activation and phosphorylation of IκBα, which mediates translocation of NF-κB into the nucleus. Overall, these results suggest that individual Sap proteins can induce an inflammatory response and that this phenomenon is independent from the pH of a specific host niche and from Sap enzymatic activity. The inflammatory response is partially dependent on Sap denaturation and is triggered by the Akt/NF-κB activation pathway. Our data suggest a novel, activity-independent aspect of Saps during interactions of C. albicans with the host.

scholarly journals Studying of biofilm formation by clinical strains of Candida albicans in interaction with Fusarium solani to predict the severity of atopic dermatitis

2020 ◽  
Vol 101 (3) ◽  
pp. 337-341
Author(s):  
S A Lisovskaya ◽  
R I Valieva ◽  
A A Sharifullina ◽  
E V Fayzullina ◽  
I M Khismatullina ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Candida Albicans ◽  
Fusarium Solani ◽  
Biofilm Formation ◽  
Film Formation ◽  
Disease Process ◽  
Skin Infections ◽  
Clinical Strains ◽  
Plate Reader ◽  
Fungus Extract

Aim. To assess the ability to form biofilms by clinical strains of the yeast Candida albicans isolated from patients with atopic dermatitis in exacerbation and remission stages under the effect of Fusarium solani micromycete and its absence. Methods. The study included 70 strains of C. albicans and one strain of F. solani. Fungal biofilms formed according to the method of Ramage. The optical density of the biofilms measured using a micro plate reader at 620 nm. The effect of associated fungi on the biofilm-forming properties of C. albicans strains was studied by an extract from opportunistic F. solani fungi. Results. The greatest biofilm formation was observed in strains isolated at the remission stage. The strains isolated in the acute period were inferior to them in the ability to form biofilms (average values of film formation were 0.143 and 0.087, respectively). Co-cultivation of C. albicans strains with F. solani fungus extract stimulated biofilm formation of C. albicans strains at a concentration of 1:10. Conclusion. This study showed a possible synergism between C. albicans and F. solani in polymicrobial skin infections, because the products of the fungus F. solani increase one of the virulence factors of the fungus C. albicans; the possibility to assess of a stimulating effect of associated fungi on the virulence one of an agent of infectious disease process will allow predicting the disease severity.

scholarly journals Metabolic Reprogramming in the Opportunistic Yeast Candida albicans in Response to Hypoxia

mSphere ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Anaïs Burgain ◽  
Faiza Tebbji ◽  
Inès Khemiri ◽  
Adnane Sellam
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Metabolic Pathways ◽  
Membrane Lipids ◽  
Oxygen Depletion ◽  
Metabolic Reprogramming ◽  
Pathogenic Yeast ◽  
Fungal Virulence ◽  
Content Type ◽  
The Impact

ABSTRACT Hypoxia is the predominant condition that the human opportunistic fungus Candida albicans encounters in the majority of the colonized niches within the host. So far, the impact of such a condition on the overall metabolism of this important human-pathogenic yeast has not been investigated. Here, we have undertaken a time-resolved metabolomics analysis to uncover the metabolic landscape of fungal cells experiencing hypoxia. Our data showed a dynamic reprogramming of many fundamental metabolic pathways, such as glycolysis, the pentose phosphate pathway, and different metabolic routes related to fungal cell wall biogenesis. The C. albicans lipidome was highly affected by oxygen depletion, with an increased level of free fatty acids and biochemical intermediates of membrane lipids, including phospholipids, lysophospholipids, sphingolipids, and mevalonate. The depletion of oxygen-dependent lipids such as ergosterol or phosphatidylcholine with longer and polyunsaturated lateral fatty acid chains was observed only at the later hypoxic time point (180 min). Transcriptomics data supported the main metabolic response to hypoxia when matched to our metabolomic profiles. The hypoxic metabolome reflected different physiological alterations of the cell wall and plasma membrane of C. albicans under an oxygen-limiting environment that were confirmed by different approaches. This study provided a framework for future in vivo investigations to examine relevant hypoxic metabolic trajectories in fungal virulence and fitness within the host. IMPORTANCE A critical aspect of cell fitness is the ability to sense and adapt to variations in oxygen levels in their local environment. Candida albicans is an opportunistic yeast that is the most prevalent human fungal pathogen. While hypoxia is the predominant condition that C. albicans encounters in most of its niches, its impact on fungal metabolism remains unexplored so far. Here, we provided a detailed landscape of the C. albicans metabolome that emphasized the importance of many metabolic routes for the adaptation of this yeast to oxygen depletion. The fungal hypoxic metabolome identified in this work provides a framework for future investigations to assess the contribution of relevant metabolic pathways in the fitness of C. albicans and other human eukaryotic pathogens with similar colonized human niches. As hypoxia is present at most of the fungal infection foci in the host, hypoxic metabolic pathways are thus an attractive target for antifungal therapy.

scholarly journals Computational and experimental approaches double the number of known introns in the pathogenic yeast Candida albicans

2007 ◽  
Vol 17 (4) ◽  
pp. 492-502 ◽  
Author(s):  
Q. M. Mitrovich ◽  
B. B. Tuch ◽  
C. Guthrie ◽  
A. D. Johnson
Keyword(s):  
Candida Albicans ◽  
Pathogenic Yeast ◽  
Experimental Approaches

scholarly journals Anti-Candida Activity of a New Platinum Derivative

2000 ◽  
Vol 44 (10) ◽  
pp. 2853-2854 ◽  
Author(s):  
T. Watanabe ◽  
M. Takano ◽  
A. Ogasawara ◽  
T. Mikami ◽  
T. Kobayashi ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Cell Membrane ◽  
Cytotoxic Activity ◽  
Mammalian Cells ◽  
Platinum Derivative

ABSTRACT A new platinum derivative of the form H[Pt(IV)(Hdigly)Cl2(OH)2] (Hdiglyglycylglycine) damaged the Candida albicans cell membrane and inhibited the growth of the cells. The cytotoxic activity of H[Pt(IV)(Hdigly)Cl2(OH)2] on mammalian cells was 10-fold lower than that ofcis-diammine-dichloroplatinum (cisplatin). Substitution of platinum for peptides is effective for enhancement of antifungal activity and reduction of the toxicity to mammalian cells.

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