Importance of Candida Antigenic Factors: Structure-Driven Immunomodulation Properties of Synthetically Prepared Mannooligosaccharides in RAW264.7 Macrophages

The incidence and prevalence of serious fungal infections is rising, especially in immunosuppressed individuals. Moreover, co-administration of antibiotics and immunosuppressants has driven the emergence of new multidrug-resistant pathogens. The significant increase of multidrug-resistant pathogens, together with their ability to form biofilms, is associated with morbidity and mortality. Research on novel synthetically prepared immunomodulators as potential antifungal immunotherapeutics is of serious interest. Our study demonstrated the immunobiological activity of synthetically prepared biotinylated mannooligosaccharides mimicking Candida antigenic factors using RAW264.7 macrophages. Macrophage exposure to the set of eight structurally different mannooligosaccharides induced a release of Th1, Th2, Th17, and Treg cytokine signature patterns. The observed immune responses were tightly associated with structure, dose, exposure time, and selected signature cytokines. The viability/cytotoxicity of the mannooligosaccharide formulas was assessed based on cell proliferation. The structure-based immunomodulatory activity of the formulas was evaluated with respect to the length, branching and conformation of the various formulas. Glycoconjugate formulas with terminal β-mannosyl-units tended to be more potent in terms of Candida relevant cytokines IL-12 p70, IL-17, GM-CSF, IL-6, and TNFα induction and cell proliferation, and this tendency was associated with structural diffe...
Source: Frontiers in cellular and infection microbiology - Category: Microbiology Source Type: research

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The cell wall is an essential component in fungal homeostasis. The lack of a covering wall in human cells makes this component an attractive target for antifungal development. The host environment and antifungal stress can lead to cell wall modifications related to drug resistance. Antifungals targeting the cell wall including the new β-D-glucan synthase inhibitor ibrexafungerp and glycosyl-phosphatidyl Inositol (GPI) anchor pathway inhibitor fosmanogepix are promising weapons against antifungal resistance. The fosmanogepix shows strong in vitro activity against the multidrug-resistant species Candida auris, Fusarium ...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
Publication date: December 2019Source: Journal of Global Antimicrobial Resistance, Volume 19Author(s): Malini R. Capoor, Chinari P. Subudhi, Andrew Collier, Abhijit M. BalAbstractAntimicrobial resistance is a global threat. To counter the growing menace of antibiotic resistance, several stewardship initiatives have been incorporated as part of the overarching strategy of healthcare delivery. In contrast, antifungal stewardship (AFS) has attracted less attention for several reasons, such as limited antifungal resistance and the lesser burden of fungal infections compared with bacterial infections. However, the emergence of ...
Source: Journal of Global Antimicrobial Resistance - Category: Infectious Diseases Source Type: research
Abstract Fungal infections are a veritable public health problem worldwide. The increasing number of patient populations at risk (e.g. transplanted individuals, cancer patients and HIV-infected people) as well as the use of antifungal agents for prophylaxis in medicine have favored the emergence of previously rare or newly identified fungal species. Indeed, novel antifungal resistance patterns have been observed, including environmental sources and the emergence of simultaneous resistance to different antifungal classes, especially in Candida spp., which are known for the multidrug-resistance (MDR) profile. In ord...
Source: Topics in HIV Medicine - Category: Infectious Diseases Authors: Tags: Curr Top Med Chem Source Type: research
Conclusion: Present study establishes a link between RTG signaling, drug efflux and biofilm formation and validates CaRTG3 as antifungal target. Intricate studies are needed to further understand and exploit this therapeutic opportunity.
Source: Journal of Medical Mycology - Category: Biology Source Type: research
Abstract Over-expression of the human P-glycoprotein (P-gp) in tumor cells is a classic example of an ABC protein serving as a hindrance to effective chemotherapy. The existence of proteins homologous to P-gp in organisms encompassing the entire living kingdom highlights extrusion of drugs as a general mechanism of multidrug resistance. Infections caused by opportunistic human fungal pathogens such as Candida species are very common and has intensified in recent years. The typical hosts, who possess suppressed immune systems due to conditions such as HIV and transplantation surgery etc., are prone to fungal infect...
Source: Fungal Genetics and Biology - Category: Biology Authors: Tags: Fungal Genet Biol Source Type: research
Publication date: Available online 11 June 2019Source: Journal of Global Antimicrobial ResistanceAuthor(s): Malini R Capoor, Chinari P Subudhi, Andrew Collier, Abhijit M BalAbstractAntimicrobial resistance is a global threat. To counter the growing menace of antibiotic resistance, several stewardship initiatives have been incorporated a part of overarching strategy of healthcare delivery. In comparison, antifungal stewardship has attracted limited attention due to several factors such as limited antifungal resistance and less burden of fungal infections compared to bacterial infections. However, emergence of resistant fung...
Source: Journal of Global Antimicrobial Resistance - Category: Infectious Diseases Source Type: research
Verónica Mixão1,2, Antonio Perez Hansen3, Ester Saus1,2, Teun Boekhout4,5, Cornelia Lass-Florl3 and Toni Gabaldón1,2,6* 1Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain 2Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain 3Division of Hygiene and Medical Microbiology, Innsbruck Medical University, Innsbruck, Austria 4Westerdijk Fungal Biodiversity Institute, Utrecht, Netherlands 5Institute of Biodiversity and Ecosystem Dynamics, University of Amsterdam, Amsterdam, Netherlands 6Institució Catalana de...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
Conclusion and Perspectives CYP51 plays a crucial role in fungal invasive growth, hyphae formation and virulence, and inhibitors targeting CYP51 have always been an important component of antifungal agents. Further researches on fungal CYP51s might set about from the following aspects: First, while the detailed crystal structures of several susceptible pathogenic fungi CYP51 have been elaborated, those of drug-resistant variants are still in hypothesis. If those structures were elucidated, targeting at common drug-resistant CYP51 protein variants could probably be promising. Second, it deserves more in-depth researches to...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
In this study, the three natural compounds 6-methoxymellein (3), angelicoin B (4) and ellagic acid as well as nine novel 3,4-dihydroisocoumarins (Figure 1) were analyzed regarding their cytotoxicity in cancer cells and inhibition of the endogenously expressed human ABC transporters P-gp, BCRP, and MRP1 and of the yeast transporter Pdr5. For further insights into the mechanism of action, Pdr5 ATPase and substrate transport assays were performed. These results were complemented with molecular docking studies that indicate that differences in the inhibitory power of the investigated 3,4-dihydroisocoumarins with respect to P-g...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Publication date: Available online 12 April 2019Source: Carbohydrate PolymersAuthor(s): Carla Vilela, Helena Oliveira, Adelaide Almeida, Armando J.D. Silvestre, Carmen S.R. FreireAbstractThe design of functional materials capable of fighting fungal infections is of paramount importance given the intricate problem of multidrug-resistant pathogenic fungi. Herein, nanocomposites consisting of cross-linked poly([2–(methacryloyloxy)ethyl] trimethylammonium chloride) (PMETAC) and bacterial nanocellulose (BNC) were prepared, characterized and tested towards the polymorphic fungus Candida albicans. The BNC three-dimensional ...
Source: Carbohydrate Polymers - Category: Biomedical Science Source Type: research
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