scholarly journals Insights Into Histoplasma capsulatum Behavior on Zinc Deprivation

Author(s):  
Leandro do Prado Assunção ◽  
Dayane Moraes ◽  
Lucas Weba Soares ◽  
Mirelle Garcia Silva-Bailão ◽  
Janaina Gomes de Siqueira ◽  
...  

Histoplasma capsulatum is a thermodimorphic fungus that causes histoplasmosis, a mycosis of global incidence. The disease is prevalent in temperate and tropical regions such as North America, South America, Europe, and Asia. It is known that during infection macrophages restrict Zn availability to H. capsulatum as a microbicidal mechanism. In this way the present work aimed to study the response of H. capsulatum to zinc deprivation. In silico analyses showed that H. capsulatum has eight genes related to zinc homeostasis ranging from transcription factors to CDF and ZIP family transporters. The transcriptional levels of ZAP1, ZRT1, and ZRT2 were induced under zinc-limiting conditions. The decrease in Zn availability increases fungicidal macrophage activity. Proteomics analysis during zinc deprivation at 24 and 48 h showed 265 proteins differentially expressed at 24 h and 68 at 48 h. Proteins related to energy production pathways, oxidative stress, and cell wall remodeling were regulated. The data also suggested that low metal availability increases the chitin and glycan content in fungal cell wall that results in smoother cell surface. Metal restriction also induces oxidative stress triggered, at least in part, by reduction in pyridoxin synthesis.

2008 ◽  
Vol 2 ◽  
pp. LPI.S1000 ◽  
Author(s):  
Marcio L. Rodrigues ◽  
Leonardo Nimrichter ◽  
Debora L. Oliveira ◽  
Joshua D. Nosanchuk ◽  
Arturo Casadevall

Fungal cells are encaged in rigid, complex cell walls. Until recently, there was remarkably little information regarding the trans-fungal cell wall transfer of intracellular macromolecules to the extracellular space. Recently, several studies have begun to elucidate the mechanisms that fungal cells utilize to secrete a wide variety of macromolecules through the cell wall. The combined use of transmission electron microscopy, serology, biochemistry, proteomics and lipidomics have revealed that the fungal pathogens Cryptococcus neoformans, Histoplasma capsulatum, Candida albicans, Candida parapsilosis and Sporothrix schenckii, as well as the model yeast Saccharomyces cerevisiae, each produces extracellular vesicles that carry lipids, proteins, polysaccharides and pigment-like structures of unquestionable biological significance. Compositional analysis of the C. neoformans and H. capsulatum extracellular vesicles suggests that they may function as ‘virulence bags’, with the potential to modulate the host-pathogen interaction in favor of the fungus. The cellular origin of the extracellular vesicles remains unknown, but morphological and biochemical features indicate that they are similar to the well-described mammalian exosomes.


2005 ◽  
Vol 4 (4) ◽  
pp. 685-693 ◽  
Author(s):  
Megan L. Bohse ◽  
Jon P. Woods

ABSTRACT The YPS3 gene of Histoplasma capsulatum encodes a protein that is both resident in the cell wall and also released into the culture medium. This protein is produced only during the pathogenic yeast phase of infection and is also expressed differently in H. capsulatum strains that differ in virulence. We investigated the cellular localization of Yps3p. We demonstrated that the cell wall fraction of Yps3p was surface localized in restriction fragment length polymorphism class 2 strains. We also established that Yps3p released into the G217B culture supernatant binds to the surface of strains that do not naturally express the protein. This binding was saturable and occurred within 5 min of exposure and occurred similarly with live and heat-killed H. capsulatum. Flow cytometric analysis of H. capsulatum after enzymatic treatments was consistent with Yps3p binding to chitin, a carbohydrate polymer that is a component of fungal cell walls. Polysaccharide binding assays demonstrated that chitin but not cellulose binds to and extracts Yps3p from culture supernatants.


2019 ◽  
Vol 19 (10) ◽  
pp. 812-830 ◽  
Author(s):  
P. Marie Arockianathan ◽  
Monika Mishra ◽  
Rituraj Niranjan

The developing resistance in fungi has become a key challenge, which is being faced nowadays with the available antifungal agents in the market. Further search for novel compounds from different sources has been explored to meet this problem. The current review describes and highlights recent advancement in the antifungal drug aspects from plant and marine based sources. The current available antifungal agents act on specific targets on the fungal cell wall, like ergosterol synthesis, chitin biosynthesis, sphingolipid synthesis, glucan synthesis etc. We discuss some of the important anti-fungal agents like azole, polyene and allylamine classes that inhibit the ergosterol biosynthesis. Echinocandins inhibit β-1, 3 glucan synthesis in the fungal cell wall. The antifungals poloxins and nikkomycins inhibit fungal cell wall component chitin. Apart from these classes of drugs, several combinatorial therapies have been carried out to treat diseases due to fungal resistance. Recently, many antifungal agents derived from plant and marine sources showed potent activity. The renewed interest in plant and marine derived compounds for the fungal diseases created a new way to treat these resistant strains which are evident from the numerous literature publications in the recent years. Moreover, the compounds derived from both plant and marine sources showed promising results against fungal diseases. Altogether, this review article discusses the current antifungal agents and highlights the plant and marine based compounds as a potential promising antifungal agents.


Author(s):  
Anna Biernasiuk ◽  
Anna Berecka-Rycerz ◽  
Anna Gumieniczek ◽  
Maria Malm ◽  
Krzysztof Z. Łączkowski ◽  
...  

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


2021 ◽  
pp. 2100110
Author(s):  
Liyuan Zhang ◽  
Mengchen Zhang ◽  
Gongping Liu ◽  
Wanqin Jin ◽  
Xiaoyan Li

Author(s):  
Giulia Maria Pires dos Santos ◽  
Gustavo Ramalho Cardoso dos Santos ◽  
Mariana Ingrid Dutra da Silva Xisto ◽  
Rodrigo Rollin-Pinheiro ◽  
Andréa Regina de Souza Baptista ◽  
...  

2017 ◽  
Vol 89 (7) ◽  
pp. 885-898 ◽  
Author(s):  
Vadim B. Krylov ◽  
Lucia Paulovičová ◽  
Ema Paulovičová ◽  
Yury E. Tsvetkov ◽  
Nikolay E. Nifantiev

AbstractThe driving force for the constant improvement and development of new synthetic methodologies in carbohydrate chemistry is a growing demand for biologically important oligosaccharide ligands and neoglycoconjugates thereof for numerous biochemical investigations such as cell-to-pathogen interactions, immune response, cell adhesion, etc. Here we report our syntheses of the spacer-armed antigenic oligosaccharides related to three groups of the polysaccharides of the fungal cell-wall including α- and β-mannan, α- and β-glucan and galactomannan chains, which include new rationally designed synthetic blocks, efficient solutions for the stereoselective construction of glycoside bonds, and novel strategy for preparation of furanoside-containing oligosaccharides based on recently discovered pyranoside-into-furanoside (PIF) rearrangement.


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