scholarly journals Chromatin-Mediated Regulation of Genome Plasticity in Human Fungal Pathogens

Genes ◽  
2019 ◽  
Vol 10 (11) ◽  
pp. 855 ◽  
Author(s):  
Buscaino
Keyword(s):  
Candida Albicans ◽  
Aspergillus Fumigatus ◽  
Cryptococcus Neoformans ◽  
Fungal Pathogens ◽  
Environmental Changes ◽  
Structure And Function ◽  
Model Systems ◽  
Genome Plasticity ◽  
And Function ◽  
Heterochromatin Structure

Human fungal pathogens, such as Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans, are a public health problem, causing millions of infections and killing almost half a million people annually. The ability of these pathogens to colonise almost every organ in the human body and cause life-threating infections relies on their capacity to adapt and thrive in diverse hostile host-niche environments. Stress-induced genome instability is a key adaptive strategy used by human fungal pathogens as it increases genetic diversity, thereby allowing selection of genotype(s) better adapted to a new environment. Heterochromatin represses gene expression and deleterious recombination and could play a key role in modulating genome stability in response to environmental changes. However, very little is known about heterochromatin structure and function in human fungal pathogens. In this review, I use our knowledge of heterochromatin structure and function in fungal model systems as a road map to review the role of heterochromatin in regulating genome plasticity in the most common human fungal pathogens: Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans.

scholarly journals Anti-Fungal Efficacy and Secondary Metabolite Analysis of the Methanolic Extract from Colpomenia peregrina towards Opportunistic Fungal Pathogens

2021 ◽  
pp. 89-100
Keyword(s):  
Candida Albicans ◽  
Aspergillus Fumigatus ◽  
Cryptococcus Neoformans ◽  
Aspergillus Flavus ◽  
Fungal Pathogens ◽  
Methanolic Extract ◽  
Chemical Shifts ◽  
Brown Seaweed ◽  
Microsporum Gypseum ◽  
Anti Fungal

The present study illustrates the antifungal efficacy of methanolic extract from marine brown seaweed Colopomenia peregrina gathered from Leepuram coast, South India, towards opportunistic fungal pathogens comprising of dermatophytes, non-dermatophytes, and yeasts. The opportunistic fungal pathogens used in the study are Aspergillus flavus (ATCC 27692), Aspergillus fumigatus (ATCC 19673), Microsporum gypseum (ATCC 24102), Cryptococcus neoformans (ATCC 14116), and Candida albicans (ATCC14053) which are commonly responsible for nosocomial infections. The NMR analysis revealed the presence of various chemical shifts showing the presence of protons containing Hydroxyl, Methoxy, Methyl groups, and –COO-CH2 groups.The presence of phytochemicals from the extract of seaweed confirmed the nutritional profile. The results revealed greater efficacy of methanolic extract towards Aspergillus fumigatus, Microsporum gypseum, Cryptococcus neoformans, and lower activity with Aspergillus flavus and Candida albicans compared with the standard anti-fungal fluconazole.

scholarly journals Islands of complex DNA are widespread in Drosophila centric heterochromatin.

Genetics ◽  
1995 ◽  
Vol 141 (1) ◽  
pp. 283-303
Author(s):  
M H Le ◽  
D Duricka ◽  
G H Karpen
Keyword(s):  
Dna Sequences ◽  
Structure And Function ◽  
Southern Analysis ◽  
Cloning And Sequencing ◽  
Pulsed Field ◽  
Drosophila Heterochromatin ◽  
And Function ◽  
Heterochromatin Structure ◽  
Derivatives Of ◽  
Eukaryotic Genomes

Abstract Heterochromatin is a ubiquitous yet poorly understood component of multicellular eukaryotic genomes. Major gaps exist in our knowledge of the nature and overall organization of DNA sequences present in heterochromatin. We have investigated the molecular structure of the 1 Mb of centric heterochromatin in the Drosophila minichromosome Dp1187. A genetic screen of irradiated minichromosomes yielded rearranged derivatives of Dp1187 whose structures were determined by pulsed-field Southern analysis and PCR. Three Dp1187 deletion derivatives and an inversion had one breakpoint in the euchromatin and one in the heterochromatin, providing direct molecular access to previously inaccessible parts of the heterochromatin. End-probed pulsed-field restriction mapping revealed the presence of at least three "islands" of complex DNA, Tahiti, Moorea, and Bora Bora, constituting approximately one half of the Dp1187 heterochromatin. Pulsed-field Southern analysis demonstrated that Drosophila heterochromatin in general is composed of alternating blocks of complex DNA and simple satellite DNA. Cloning and sequencing of a small part of one island, Tahiti, demonstrated the presence of a retroposon. The implications of these findings to heterochromatin structure and function are discussed.

scholarly journals Dectin-2-Targeted Antifungal Liposomes Exhibit Enhanced Efficacy

mSphere ◽  
2019 ◽  
Vol 4 (5) ◽  
Author(s):  
Suresh Ambati ◽  
Emma C. Ellis ◽  
Jianfeng Lin ◽  
Xiaorong Lin ◽  
Zachary A. Lewis ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Aspergillus Fumigatus ◽  
Effective Dose ◽  
Cryptococcus Neoformans ◽  
Amphotericin B ◽  
Antifungal Drugs ◽  
Extracellular Matrices ◽  
Content Type ◽  
Order Of Magnitude ◽  
Life Threatening

ABSTRACT Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus cause life-threatening candidiasis, cryptococcosis, and aspergillosis, resulting in several hundred thousand deaths annually. The patients at the greatest risk of developing these life-threatening invasive fungal infections have weakened immune systems. The vulnerable population is increasing due to rising numbers of immunocompromised individuals as a result of HIV infection or immunosuppressed individuals receiving anticancer therapies and/or stem cell or organ transplants. While patients are treated with antifungals such as amphotericin B, all antifungals have serious limitations due to lack of sufficient fungicidal effect and/or host toxicity. Even with treatment, 1-year survival rates are low. We explored methods of increasing drug effectiveness by designing fungicide-loaded liposomes specifically targeted to fungal cells. Most pathogenic fungi are encased in cell walls and exopolysaccharide matrices rich in mannans. Dectin-2 is a mammalian innate immune membrane receptor that binds as a dimer to mannans and signals fungal infection. We coated amphotericin-loaded liposomes with monomers of Dectin-2’s mannan-binding domain, sDectin-2. sDectin monomers were free to float in the lipid membrane and form dimers that bind mannan substrates. sDectin-2-coated liposomes bound orders of magnitude more efficiently to the extracellular matrices of several developmental stages of C. albicans, C. neoformans, and A. fumigatus than untargeted control liposomes. Dectin-2-coated amphotericin B-loaded liposomes reduced the growth and viability of all three species more than an order of magnitude more efficiently than untargeted control liposomes and dramatically decreased the effective dose. Future efforts focus on examining pan-antifungal targeted liposomal drugs in animal models of fungal diseases. IMPORTANCE Invasive fungal diseases caused by Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus have mortality rates ranging from 10 to 95%. Individual patient costs may exceed $100,000 in the United States. All antifungals in current use have serious limitations due to host toxicity and/or insufficient fungal cell killing that results in recurrent infections. Few new antifungal drugs have been introduced in the last 2 decades. Hence, there is a critical need for improved antifungal therapeutics. By targeting antifungal-loaded liposomes to α-mannans in the extracellular matrices secreted by these fungi, we dramatically reduced the effective dose of drug. Dectin-2-coated liposomes loaded with amphotericin B bound 50- to 150-fold more strongly to C. albicans, C. neoformans, and A. fumigatus than untargeted liposomes and killed these fungi more than an order of magnitude more efficiently. Targeting drug-loaded liposomes specifically to fungal cells has the potential to greatly enhance the efficacy of most antifungal drugs.

scholarly journals Novel Antifungal Compounds Discovered in Medicines for Malaria Venture’s Malaria Box

mSphere ◽  
2018 ◽  
Vol 3 (2) ◽  
Author(s):  
Eric H. Jung ◽  
David J. Meyers ◽  
Jürgen Bosch ◽  
Arturo Casadevall
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Cryptococcus Neoformans ◽  
Fungal Pathogens ◽  
Pathogenic Fungi ◽  
Cryptococcus Gattii ◽  
Antifungal Drugs ◽  
Resistant Bacteria ◽  
Animal Cells ◽  
Malaria Box

ABSTRACTSimilarities in fungal and animal cells make antifungal discovery efforts more difficult than those for other classes of antimicrobial drugs. Currently, there are only three major classes of antifungal drugs used for the treatment of systemic fungal diseases: polyenes, azoles, and echinocandins. Even in situations where the offending fungal organism is susceptible to the available drugs, treatment courses can be lengthy and unsatisfactory, since eradication of infection is often very difficult, especially in individuals with impaired immunity. Consequently, there is a need for new and more effective antifungal drugs. We have identified compounds with significant antifungal activity in the Malaria Box (Medicines for Malaria Ventures, Geneva, Switzerland) that have higher efficacy than some of the currently used antifungal drugs. Our best candidate, MMV665943 (IUPAC name 4-[6-[[2-(4-aminophenyl)-3H-benzimidazol-5-yl]methyl]-1H-benzimidazol-2-yl]aniline), here referred to as DM262, showed 16- to 32-fold-higher activity than fluconazole againstCryptococcus neoformans. There was also significant antifungal activity in other fungal species with known antifungal resistance, such asLomentospora prolificansandCryptococcus gattii. Antifungal activity was also observed against a common fungus,Candida albicans. These results are important because they offer a potentially new class of antifungal drugs and the repurposing of currently available therapeutics.IMPORTANCEMuch like the recent increase in drug-resistant bacteria, there is a rise in antifungal-resistant strains of pathogenic fungi. There is a need for novel and more potent antifungal therapeutics. Consequently, we investigated a mixed library of drug-like and probe-like compounds with activity inPlasmodiumspp. for activity against two common fungal pathogens,Cryptococcus neoformansandCandida albicans, along with two less common pathogenic species,Lomentospora prolificansandCryptococcus gattii. We uncover a previously uncharacterized drug with higher broad-spectrum antifungal activity than some current treatments. Our findings may eventually lead to a compound added to the arsenal of antifungal therapeutics.

scholarly journals Advances in Understanding the Acyl-CoA-Binding Protein in Plants, Mammals, Yeast, and Filamentous Fungi

2020 ◽  
Vol 6 (1) ◽  
pp. 34
Author(s):  
Shangkun Qiu ◽  
Bin Zeng
Keyword(s):  
Arabidopsis Thaliana ◽  
Oryza Sativa ◽  
Filamentous Fungi ◽  
Fungal Pathogens ◽  
Binding Protein ◽  
Structure And Function ◽  
Monascus Ruber ◽  
Binding Characteristics ◽  
And Function ◽  
High Binding Affinity

Acyl-CoA-binding protein (ACBP) is an important protein with a size of about 10 kDa. It has a high binding affinity for C12–C22 acyl-CoA esters and participates in lipid metabolism. ACBP and its family of proteins have been found in all eukaryotes and some prokaryotes. Studies have described the function and structure of ACBP family proteins in mammals (such as humans and mice), plants (such as Oryza sativa, Arabidopsis thaliana, and Hevea brasiliensis) and yeast. However, little information on the structure and function of the proteins in filamentous fungi has been reported. This article concentrates on recent advances in the research of the ACBP family proteins in plants and mammals, especially in yeast, filamentous fungi (such as Monascus ruber and Aspergillus oryzae), and fungal pathogens (Aspergillus flavus, Cryptococcus neoformans). Furthermore, we discuss some problems in the field, summarize the binding characteristics of the ACBP family proteins in filamentous fungi and yeast, and consider the future of ACBP development.

Control of Metal Nanocrystal Size Reveals Metal-Support Interface Role for Ceria Catalysts

Science ◽  
2013 ◽  
Vol 341 (6147) ◽  
pp. 771-773 ◽  
Author(s):  
Matteo Cargnello ◽  
Vicky V. T. Doan-Nguyen ◽  
Thomas R. Gordon ◽  
Rosa E. Diaz ◽  
Eric A. Stach ◽  
...  
Keyword(s):  
Carbon Monoxide ◽  
Structure And Function ◽  
Nanocrystal Size ◽  
Model Systems ◽  
Group Viii ◽  
Metal Interface ◽  
Platinum Nanocrystals ◽  
Metal Support ◽  
Ceria Catalysts ◽  
And Function

Interactions between ceria (CeO2) and supported metals greatly enhance rates for a number of important reactions. However, direct relationships between structure and function in these catalysts have been difficult to extract because the samples studied either were heterogeneous or were model systems dissimilar to working catalysts. We report rate measurements on samples in which the length of the ceria-metal interface was tailored by the use of monodisperse nickel, palladium, and platinum nanocrystals. We found that carbon monoxide oxidation in ceria-based catalysts is greatly enhanced at the ceria-metal interface sites for a range of group VIII metal catalysts, clarifying the pivotal role played by the support.

Cross-protective TH1 immunity against Aspergillus fumigatus and Candida albicans

Blood ◽  
2011 ◽  
Vol 117 (22) ◽  
pp. 5881-5891 ◽  
Author(s):  
Claudia Stuehler ◽  
Nina Khanna ◽  
Silvia Bozza ◽  
Teresa Zelante ◽  
Silvia Moretti ◽  
...  
Keyword(s):  
Candida Albicans ◽  
T Cell ◽  
Aspergillus Fumigatus ◽  
Fungal Pathogens ◽  
Cell Receptor ◽  
Cross Protection ◽  
Th1 Cells ◽  
Receptor Repertoire ◽  
Immunogenic Epitope ◽  
Severe Infections

AbstractT cell–mediated heterologous immunity to different pathogens is promising for the development of immunotherapeutic strategies. Aspergillus fumigatus and Candida albicans, the 2 most common fungal pathogens causing severe infections in immunocompromised patients, are controlled by CD4+ type 1 helper T (TH1) cells in humans and mice, making induction of fungus-specific CD4+ TH1 immunity an appealing strategy for antifungal therapy. We identified an immunogenic epitope of the A fumigatus cell wall glucanase Crf1 that can be presented by 3 common major histocompatibility complex class II alleles and that induces memory CD4+ TH1 cells with a diverse T-cell receptor repertoire that is cross-reactive to C albicans. In BALB/c mice, the Crf1 protein also elicits cross-protection against lethal infection with C albicans that is mediated by the same epitope as in humans. These data illustrate the existence of T cell–based cross-protection for the 2 distantly related clinically relevant fungal pathogens that may foster the development of immunotherapeutic strategies.

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