Lipid peroxidation by alveolar macrophages challenged with Cryptococcus neoformans, Candida albicans or Aspergillus fumigatus

2000 ◽  
Vol 38 (6) ◽  
pp. 443-449 ◽  
Author(s):  
N. T. Gross ◽  
K. Hultenby ◽  
S. Mengarelli ◽  
P. Camner ◽  
C. Jarstrand
Keyword(s):  
Lipid Peroxidation ◽  
Candida Albicans ◽  
Aspergillus Fumigatus ◽  
Cryptococcus Neoformans ◽  
Alveolar Macrophages

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 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 Candida albicans, Cryptococcus neoformans or Aspergillus fumigatus Induces an Antifungal Activity in Mouse Serum, which is Different from Transferrin

2009 ◽  
Vol 71 (11) ◽  
pp. 1459-1464
Author(s):  
Ken-ichi OKAZAKI ◽  
Masahiro ASAKURA ◽  
Norihiko SUGIMOTO ◽  
Atsushi HINENOYA ◽  
Shinji YAMASAKI
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Aspergillus Fumigatus ◽  
Cryptococcus Neoformans ◽  
Mouse Serum

Neues zu opportunistischen Infektionen des zentralen Nervensystems bei iatrogener Immunsuppression

2017 ◽  
Vol 45 (05) ◽  
pp. 370-380
Author(s):  
Gabriele Arendt ◽  
Matthias Maschke
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Candida Albicans ◽  
Listeria Monocytogenes ◽  
Toxoplasma Gondii ◽  
Aspergillus Fumigatus ◽  
Cryptococcus Neoformans ◽  
Jc Virus ◽  
Nocardia Asteroides ◽  
Bakterielle Infektionen ◽  
Opportunistische Infektionen

ZusammenfassungOpportunistische Infektionen des zentralen Nervensystems (ZNS) mit infolge einer iatrogenen Immunsuppression auftretenden Virus-, Parasiten-, Pilz- oder Bakterien-induzierten Erkrankungen sind bei der steigenden Zahl an Patienten mit Organtransplantationen oder immunmodulierenden Therapien von großer medizinischer Bedeutung. Hauptsächliche Anwender dieser modernen Behandlungsformen sind neben der Transplantationsmedizin die Dermatologie (Interferone, Rituximab, Fingolimod u. a.), Hämato-/Onkologie (Rituximab u. a.), Neurologie (Beta-Interferon, Glatirameracetat, Natalizumab, Rituximab, Teriflunomid, Fingolimod, Alemtuzumab, Daclizumab u. a.) und Rheumatologie (Rituximab u. a.).Das Keimspektrum bei iatrogener Immunsuppression in Europa umfasst in der Hauptsache Viren der Herpesgruppe sowie insbesondere bei immunmodulatorisch behandelten Patienten das JC-Virus (JCV); an Pilzerregern sind Aspergillus fumigatus, Candida albicans und Cryptococcus neoformans von Bedeutung. Eine wichtige parasitäre Infektion ist die mit Toxoplasma gondii (T. g.). Typische bakterielle Infektionen des iatrogen immunkompromittierten Patienten werden durch Nocardia asteroides, Listeria monocytogenes und Mycobacterium tuberculosis hervorgerufen.Es werden typische diagnostische Konstellationen und Therapien vorgestellt.

scholarly journals Fungi pathogenic to humans: molecular bases of virulence of Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus.

2009 ◽  
Vol 56 (2) ◽  
Author(s):  
Justyna Karkowska-Kuleta ◽  
Maria Rapala-Kozik ◽  
Andrzej Kozik
Keyword(s):  
Candida Albicans ◽  
Aspergillus Fumigatus ◽  
Cryptococcus Neoformans ◽  
Virulence Factors ◽  
Immunosuppressive Agents ◽  
Hydrolytic Enzymes ◽  
Host Cells ◽  
Phenotypic Switching ◽  
Human Organism ◽  
Fungal Virulence

The frequency of severe systemic fungal diseases has increased in the last few decades. The clinical use of antibacterial drugs, immunosuppressive agents after organ transplantation, cancer chemotherapy, and advances in surgery are associated with increasing risk of fungal infections. Opportunistic pathogens from the genera Candida and Aspergillus as well as pathogenic fungi from the genus Cryptococcus can invade human organism and may lead to mucosal and skin infections or to deep-seated mycoses of almost all inner organs, especially in immunocompromised patients. Nowadays, there are some effective antifungal agents, but, unfortunately, some of the pathogenic species show increasing resistance. The identification of fungal virulence factors and recognition of mechanisms of pathogenesis may lead to development of new efficient antifungal therapies. This review is focused on major virulence factors of the most common fungal pathogens of humans: Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans. The adherence to host cells and tissues, secretion of hydrolytic enzymes, phenotypic switching and morphological dimorphism contribute to C. albicans virulence. The ability to grow at 37 degrees C, capsule synthesis and melanin formation are important virulence factors of C. neoformans. The putative virulence factors of A. fumigatus include production of pigments, adhesion molecules present on the cell surface and secretion of hydrolytic enzymes and toxins.

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.

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