scholarly journals Rare and Emerging Opportunistic Fungal Pathogens: Concern for Resistance beyond Candida albicans and Aspergillus fumigatus

2004 ◽  
Vol 42 (10) ◽  
pp. 4419-4431 ◽  
Author(s):  
M. A. Pfaller ◽  
D. J. Diekema
Genes ◽  
2019 ◽  
Vol 10 (11) ◽  
pp. 855 ◽  
Author(s):  
Buscaino

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.


Blood ◽  
2011 ◽  
Vol 117 (22) ◽  
pp. 5881-5891 ◽  
Author(s):  
Claudia Stuehler ◽  
Nina Khanna ◽  
Silvia Bozza ◽  
Teresa Zelante ◽  
Silvia Moretti ◽  
...  

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.


2011 ◽  
Vol 11 (2) ◽  
pp. 98-108 ◽  
Author(s):  
Michelle D. Leach ◽  
Alistair J. P. Brown

ABSTRACTPosttranslational modifications of proteins drive a wide variety of cellular processes in eukaryotes, regulating cell growth and division as well as adaptive and developmental processes. With regard to the fungal kingdom, most information about posttranslational modifications has been generated through studies of the model yeastsSaccharomyces cerevisiaeandSchizosaccharomyces pombe, where, for example, the roles of protein phosphorylation, glycosylation, acetylation, ubiquitination, sumoylation, and neddylation have been dissected. More recently, information has begun to emerge for the medically important fungal pathogensCandida albicans,Aspergillus fumigatus, andCryptococcus neoformans, highlighting the relevance of posttranslational modifications for virulence. We review the available literature on protein modifications in fungal pathogens, focusing in particular upon the reversible peptide modifications sumoylation, ubiquitination, and neddylation.


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.


mSphere ◽  
2019 ◽  
Vol 4 (5) ◽  
Author(s):  
Suresh Ambati ◽  
Emma C. Ellis ◽  
Jianfeng Lin ◽  
Xiaorong Lin ◽  
Zachary A. Lewis ◽  
...  

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.


Viruses ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 686
Author(s):  
Hasan Nazik ◽  
Ioly Kotta-Loizou ◽  
Gabriele Sass ◽  
Robert H. A. Coutts ◽  
David A. Stevens

Aspergillus and Pseudomonas compete in nature, and are the commonest bacterial and fungal pathogens in some clinical settings, such as the cystic fibrosis lung. Virus infections of fungi occur naturally. Effects on fungal physiology need delineation. A common reference Aspergillus fumigatus strain, long studied in two (of many) laboratories, was found infected with the AfuPmV-1 virus. One isolate was cured of virus, producing a virus-free strain. Virus from the infected strain was purified and used to re-infect three subcultures of the virus-free fungus, producing six fungal strains, otherwise isogenic. They were studied in intermicrobial competition with Pseudomonasaeruginosa. Pseudomonas culture filtrates inhibited forming or preformed Aspergillus biofilm from infected strains to a greater extent, also seen when Pseudomonas volatiles were assayed on Aspergillus. Purified iron-chelating Pseudomonas molecules, known inhibitors of Aspergillus biofilm, reproduced these differences. Iron, a stimulus of Aspergillus, enhanced the virus-free fungus, compared to infected. All infected fungal strains behaved similarly in assays. We show an important consequence of virus infection, a weakening in intermicrobial competition. Viral infection may affect the outcome of bacterial–fungal competition in nature and patients. We suggest that this occurs via alteration in fungal stress responses, the mechanism best delineated here is a result of virus-induced altered Aspergillus iron metabolism.


2021 ◽  
Author(s):  
Mahdi Hosseini Bafghi ◽  
Razieh Nazari ◽  
Majid Darroudi ◽  
Mohsen Zargar ◽  
Hossein Zarrinfar

Abstract Biosynthesis of nanoparticles can stand as a replacement for the available chemical and physical methods by offering new procedures as green syntheses that have proved to be simple, biocompatible, safe, and cost-effective. Considering how nanoparticles with a size of 1 to 100 nanometers contain unique physical and chemical properties, recent reports are indicative of observing the antifungal qualities of selenium nanoparticles (Se-NPs). Recently, the observance of antifungal resistance towards different species of these fungi is often reported. Therefore, due to the antifungal effects of biological nanoparticles, this study aimed to investigate the exertion of these nanoparticles and evaluate their effects on the growth of fungal pathogens. Se-NPs were biosynthesized by the application of wet reduction method, which included specific concentrations of Aspergillus flavus and Candida albicans. The presence of nanoparticles was confirmed by methods such as UV-Vis spectroscopy, FT-IR analysis, and FESEM electron microscope that involved FESEM and EDAX diagram. The fungal strains were cultured in sabouraud dextrose agar medium to perform the sensitivity test based on the minimum inhibitory concentration (MIC) method in duplicate. The utilization of Se-NPs at concentrations of 1 µg/ ml and below resulted in zero growth of fungal agents. However, their growth was inhibited by antifungal drugs at concentrations of 2 µg/ ml and higher. Based on the obtained results, biological nanoparticles produced by fungal agents at different concentrations exhibited favorable inhibitory effects on the growth of fungal strains.


2011 ◽  
Vol 35 (1) ◽  
pp. 167-173
Author(s):  
Rusol Muhammedi Al Bahran

The study included 100 samples collected from different locations of the homes were located in the area of Ali Saleh in Baghdad 6 species were isolated from fungi and the most common genus or species of fungi isolated were Aspergillus fumigatus by frequency ratio of 25.84%, and occurrence ratio of 23%, Penicilium by frequency ratio of 21.34%, and occurrence ratio of 19%, Mucor by frequency ratio 20.22%, and the occurrence ratio of 18%, Candida albicans by frequency ratio of 15.73%, the occurrence ratio of 14%, Rhizopus frequency ratio by 13.48%, the occurrence ratio of 12% and Aspergillus niger frequency ratio by 3.37% and the occurrence ratio of 3%. Then the sensitivity test of disinfectants were studied against fungi isolated by using three disinfectants Chloroxylenol known commercially by (Dettol), Chlorhexidine commercially known by (Hibitane) and Sodium hypochlorite commercially known by (Bleach), and a study for the effected of three concentrations of each disinfectant (5, 2.5, 1.25)%, and the use of statistical analysis (ANOVA) to contrast the differences and Dnken test to the variation in any disinfectant or the most efficient concentrations of other disinfectants were observed that concentrations of 5% was the most efficient of concentrations than (2.5%) and (1.25%). As the disinfectant Dettol was significantly the most efficient from Bleach and Hibitane.


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