scholarly journals Applications of Invertebrate Animal Models to Dimorphic Fungal Infections

2018 ◽  
Vol 4 (4) ◽  
pp. 118 ◽  
Author(s):  
Junya L. Singulani ◽  
Liliana Scorzoni ◽  
Haroldo C. de Oliveira ◽  
Caroline M. Marcos ◽  
Patricia A. Assato ◽  
...  
Keyword(s):  
Animal Models ◽  
Histoplasma Capsulatum ◽  
Galleria Mellonella ◽  
Ethical Issues ◽  
Fungal Infections ◽  
Low Cost ◽  
Acanthamoeba Castellanii ◽  
Dimorphic Fungi ◽  
Invertebrate Animal ◽  
Different Strains

Dimorphic fungi can be found in the yeast form during infection and as hyphae in the environment and are responsible for a large number of infections worldwide. Invertebrate animals have been shown to be convenient models in the study of fungal infections. These models have the advantages of being low cost, have no ethical issues, and an ease of experimentation, time-efficiency, and the possibility of using a large number of animals per experiment compared to mammalian models. Invertebrate animal models such as Galleria mellonella, Caenorhabditis elegans, and Acanthamoeba castellanii have been used to study dimorphic fungal infections in the context of virulence, innate immune response, and the efficacy and toxicity of antifungal agents. In this review, we first summarize the features of these models. In this aspect, the growth temperature, genome sequence, availability of different strains, and body characteristics should be considered in the model choice. Finally, we discuss the contribution and advances of these models, with respect to dimorphic fungi Paracoccidioides spp., Histoplasma capsulatum, Blastomyces dermatitidis, Sporothrix spp., and Talaromyces marneffei (Penicillium marneffei).

scholarly journals Immune Response of Galleria mellonella against Human Fungal Pathogens

2018 ◽  
Vol 5 (1) ◽  
pp. 3 ◽  
Author(s):  
Nuria Trevijano-Contador ◽  
Oscar Zaragoza
Keyword(s):  
Immune Response ◽  
Fungal Pathogens ◽  
Histoplasma Capsulatum ◽  
Galleria Mellonella ◽  
Low Cost ◽  
Innate Immune ◽  
Human Pathogens ◽  
Lytic Enzymes ◽  
Wide Range ◽  
Great Specificity

In many aspects, the immune response against pathogens in insects is similar to the innate immunity in mammals. This has caused a strong interest in the scientific community for the use of this model in research of host–pathogen interactions. In recent years, the use of Galleria mellonella larvae, an insect belonging to the Lepidoptera order, has emerged as an excellent model to study the virulence of human pathogens. It is a model that offers many advantages; for example, it is easy to handle and establish in every laboratory, the larvae have a low cost, and they tolerate a wide range of temperatures, including human temperature 37 °C. The immune response of G. mellonella is innate and is divided into a cellular component (hemocytes) and humoral component (antimicrobial peptides, lytic enzymes, and peptides and melanin) that work together against different intruders. It has been shown that the immune response of this insect has a great specificity and has the ability to distinguish between different classes of microorganisms. In this review, we delve into the different components of the innate immune response of Galleria mellonella, and how these components manifest in the infection of fungal pathogens including Candida albicans, Aspergillus fumigatus, Cryptococcus neoformans, and Histoplasma capsulatum.

scholarly journals Current status of in vitro and in vivo antifungal activities of posaconazole

2013 ◽  
Vol 1 (1) ◽  
pp. 18-22
Author(s):  
He Sun ◽  
Xin Su ◽  
Yi Shi
Keyword(s):  
Animal Models ◽  
Broad Spectrum ◽  
Fungal Infections ◽  
Current Status ◽  
Dimorphic Fungi ◽  
Antifungal Activities ◽  
Endemic Fungi ◽  
Yeasts And Molds

Abstract Posaconazole (POS) is a new triazole drug with broad-spectrum in vitro activity against most yeasts and molds such as Candida, Cryptococcus neoformans, Aspergillus, Fusarium and Zygomycetes, as well as certain species of dimorphic fungi and endemic fungi. In immunocompetent or immunocompromised animal models with invasive fungal infections, POS has demonstrated highly effective, broad-spectrum antifungal activities. In vitro and in vivo antifungal activities of POS were superior to those of other azoles against Candida glabrata, Candida krusei, Aspergillus terrus, Fusarium and Zygomycetes. In vivo susceptibility studies have shown promising efficacy of POS against life-threatening fungal infections in animal models with different immune status and infection sites.

scholarly journals Interaction of Blastomyces dermatitidis, Sporothrix schenckii, and Histoplasma capsulatum with Acanthamoeba castellanii

2004 ◽  
Vol 72 (6) ◽  
pp. 3478-3488 ◽  
Author(s):  
Judith N. Steenbergen ◽  
Joshua D. Nosanchuk ◽  
Stephanie D. Malliaris ◽  
Arturo Casadevall
Keyword(s):  
Histoplasma Capsulatum ◽  
Sporothrix Schenckii ◽  
Acanthamoeba Castellanii ◽  
Fungal Growth ◽  
Laboratory Strain ◽  
Yeast Cells ◽  
Blastomyces Dermatitidis ◽  
Mammalian Host ◽  
Human Pathogens ◽  
Dimorphic Fungi

ABSTRACT Several dimorphic fungi are important human pathogens, but the origin and maintenance of virulence in these organisms is enigmatic, since an interaction with a mammalian host is not a requisite for fungal survival. Recently, Cryptococcus neoformans was shown to interact with macrophages, slime molds, and amoebae in a similar manner, suggesting that fungal pathogenic strategies may arise from environmental interactions with phagocytic microorganisms. In this study, we examined the interactions of three dimorphic fungi with the soil amoeba Acanthameobae castellanii. Yeast forms of Blastomyces dermatitidis, Sporothrix schenckii, and Histoplasma capsulatum were each ingested by amoebae and macrophages, and phagocytosis of yeast cells resulted in amoeba death and fungal growth. H. capsulatum conidia were also cytotoxic to amoebae. For each fungal species, exposure of yeast cells to amoebae resulted in an increase in hyphal cells. Exposure of an avirulent laboratory strain of H. capsulatum to A. castellanii selected for, or induced, a phenotype of H. capsulatum that caused a persistent murine lung infection. These results are consistent with the view that soil amoebae may contribute to the selection and maintenance of certain traits in pathogenic dimorphic fungi that confer on these microbes the capacity for virulence in mammals.

Endemic Fungi Presenting as Community-Acquired Pneumonia: A Review

2020 ◽  
Vol 41 (04) ◽  
pp. 522-537
Author(s):  
Marwan M. Azar ◽  
Joshua Malo ◽  
Chadi A. Hage
Keyword(s):  
Histoplasma Capsulatum ◽  
Fungal Infections ◽  
Treatment Strategies ◽  
Community Acquired Pneumonia ◽  
Land Utilization ◽  
Coccidioides Posadasii ◽  
Dimorphic Fungi ◽  
Pulmonary Histoplasmosis ◽  
Diagnostic Modalities ◽  
Endemic Fungi

AbstractIn endemic areas, dimorphic fungal infections due to Histoplasma capsulatum, Blastomyces dermatitidis, and Coccidioides posadasii/immitis account for up to 30% of cases of community-acquired pneumonia. Because respiratory manifestations are often indistinguishable from common bacterial causes of pneumonia, the diagnosis of pulmonary histoplasmosis, blastomycosis, and coccidioidomycosis is often delayed and associated with antibiotics overuse. In addition to being highly endemic to certain regions of North America, dimorphic fungi have global significance due to established areas of endemicity in all six inhabited continents, an increasingly interconnected world of travelers and transported goods, and a changing epidemiology as a result of global heating and anthropomorphic land utilization. In this review, we discuss the epidemiology, pathogenesis, clinical presentation, diagnostic modalities, and treatment strategies for histoplasmosis, blastomycosis, and coccidioidomycosis.

scholarly journals Direct Visualization of Fungal Burden in Filamentous Fungus-Infected Silkworms

2021 ◽  
Vol 7 (2) ◽  
pp. 136
Author(s):  
Yidong Yu ◽  
Ann-Katrin Wolf ◽  
Sina Thusek ◽  
Thorsten Heinekamp ◽  
Michael Bromley ◽  
...  
Keyword(s):  
Animal Models ◽  
Large Scale ◽  
Ethical Issues ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
Infection Model ◽  
Calcofluor White ◽  
Fungal Pathogenicity ◽  
Staining Protocol

Invasive fungal infections (IFIs) are difficult to diagnose and to treat and, despite several available antifungal drugs, cause high mortality rates. In the past decades, the incidence of IFIs has continuously increased. More recently, SARS-CoV-2-associated lethal IFIs have been reported worldwide in critically ill patients. Combating IFIs requires a more profound understanding of fungal pathogenicity to facilitate the development of novel antifungal strategies. Animal models are indispensable for studying fungal infections and to develop new antifungals. However, using mammalian animal models faces various hurdles including ethical issues and high costs, which makes large-scale infection experiments extremely challenging. To overcome these limitations, we optimized an invertebrate model and introduced a simple calcofluor white (CW) staining protocol to macroscopically and microscopically monitor disease progression in silkworms (Bombyx mori) infected with the human pathogenic filamentous fungi Aspergillus fumigatus and Lichtheimia corymbifera. This advanced silkworm A. fumigatus infection model could validate knockout mutants with either attenuated, strongly attenuated or unchanged virulence. Finally, CW staining allowed us to efficiently visualize antifungal treatment outcomes in infected silkworms. Conclusively, we here present a powerful animal model combined with a straightforward staining protocol to expedite large-scale in vivo research of fungal pathogenicity and to investigate novel antifungal candidates.

scholarly journals Newly Isolated Animal Pathogen Corynebacterium silvaticum Is Cytotoxic to Human Epithelial Cells

2021 ◽  
Vol 22 (7) ◽  
pp. 3549
Author(s):  
Jens Möller ◽  
Anne Busch ◽  
Christian Berens ◽  
Helmut Hotzel ◽  
Andreas Burkovski
Keyword(s):  
Cell Lines ◽  
Galleria Mellonella ◽  
Roe Deer ◽  
Electric Resistance ◽  
Human Epithelial Cell ◽  
Cytotoxicity Assays ◽  
Corynebacterium Ulcerans ◽  
Invertebrate Animal ◽  
Epithelial Cell Lines ◽  
Microscopy Measurement

Corynebacterium silvaticum is a newly identified animal pathogen of forest animals such as roe deer and wild boars. The species is closely related to the emerging human pathogen Corynebacterium ulcerans and the widely distributed animal pathogen Corynebacterium pseudotuberculosis. In this study, Corynebacterium silvaticum strain W25 was characterized with respect to its interaction with human cell lines. Microscopy, measurement of transepithelial electric resistance and cytotoxicity assays revealed detrimental effects of C. silvaticum to different human epithelial cell lines and to an invertebrate animal model, Galleria mellonella larvae, comparable to diphtheria toxin-secreting C. ulcerans. Furthermore, the results obtained may indicate a considerable zoonotic potential of this newly identified species.

scholarly journals Techniques for the Assessment of In Vitro and In Vivo Antifungal Combinations

2021 ◽  
Vol 7 (2) ◽  
pp. 113
Author(s):  
Anne-Laure Bidaud ◽  
Patrick Schwarz ◽  
Guillaume Herbreteau ◽  
Eric Dannaoui
Keyword(s):  
Animal Models ◽  
Fungal Infections ◽  
Acquired Resistance ◽  
Adequate Treatment ◽  
Combination Treatments ◽  
Target Organs ◽  
Fungal Load ◽  
Time Kill

Systemic fungal infections are associated with high mortality rates despite adequate treatment. Moreover, acquired resistance to antifungals is increasing, which further complicates the therapeutic management. One strategy to overcome antifungal resistance is to use antifungal combinations. In vitro, several techniques are used to assess drug interactions, such as the broth microdilution checkerboard, agar-diffusion methods, and time-kill curves. Currently, the most widely used technique is the checkerboard method. The aim of all these techniques is to determine if the interaction between antifungal agents is synergistic, indifferent, or antagonistic. However, the interpretation of the results remains difficult. Several methods of analysis can be used, based on different theories. The most commonly used method is the calculation of the fractional inhibitory concentration index. Determination of the usefulness of combination treatments in patients needs well-conducted clinical trials, which are difficult. It is therefore important to study antifungal combinations in vivo, in experimental animal models of fungal infections. Although mammalian models have mostly been used, new alternative animal models in invertebrates look promising. To evaluate the antifungal efficacy, the most commonly used criteria are the mortality rate and the fungal load in the target organs.

scholarly journals Characterisation of a highly potent and near pan-neutralising anti-HIV monoclonal antibody expressed in tobacco plants

Retrovirology ◽  
2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Catherine M. Moore ◽  
Melanie Grandits ◽  
Clemens Grünwald-Gruber ◽  
Friedrich Altmann ◽  
Maria Kotouckova ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Low Cost ◽  
Leaf Tissue ◽  
Glycosylation Site ◽  
People Living With Hiv ◽  
Middle Income ◽  
Effector Cells ◽  
Extraction And Purification ◽  
Important Health ◽  
Different Strains

Abstract Background HIV remains one of the most important health issues worldwide, with almost 40 million people living with HIV. Although patients develop antibodies against the virus, its high mutation rate allows evasion of immune responses. Some patients, however, produce antibodies that are able to bind to, and neutralise different strains of HIV. One such ‘broadly neutralising’ antibody is ‘N6’. Identified in 2016, N6 can neutralise 98% of HIV-1 isolates with a median IC50 of 0.066 µg/mL. This neutralisation breadth makes N6 a very promising therapeutic candidate. Results N6 was expressed in a glycoengineered line of N. benthamiana plants (pN6) and compared to the mammalian cell-expressed equivalent (mN6). Expression at 49 mg/kg (fresh leaf tissue) was achieved in plants, although extraction and purification are more challenging than for most plant-expressed antibodies. N-glycoanalysis demonstrated the absence of xylosylation and a reduction in α(1,3)-fucosylation that are typically found in plant glycoproteins. The N6 light chain contains a potential N-glycosylation site, which was modified and displayed more α(1,3)-fucose than the heavy chain. The binding kinetics of pN6 and mN6, measured by surface plasmon resonance, were similar for HIV gp120. pN6 had a tenfold higher affinity for FcγRIIIa, which was reflected in an antibody-dependent cellular cytotoxicity assay, where pN6 induced a more potent response from effector cells than that of mN6. pN6 demonstrated the same potency and breadth of neutralisation as mN6, against a panel of HIV strains. Conclusions The successful expression of N6 in tobacco supports the prospect of developing a low-cost, low-tech production platform for a monoclonal antibody cocktail to control HIV in low-to middle income countries. Graphic abstract

scholarly journals Ethical Issues in Global Supply Chains

2007 ◽  
Author(s):  
Bodo B. Schlegelmilch ◽  
Magdalena Öberseder
Keyword(s):  
Supply Chain ◽  
Supply Chains ◽  
Working Conditions ◽  
Ethical Issues ◽  
Low Cost ◽  
Global Supply Chains ◽  
Unethical Conduct ◽  
Production Methods ◽  
Technological Advances ◽  
Consumer Demands

Despite all technological advances, global supply chains are always based on the interaction of people. And wherever people interact, a kaleidoscope of ethical issues emerges. While consumer demands and concerns have undoubtedly led to an increased awareness of unethical conduct in the supply chain, contravening forces, such as the relentless pressures for low cost products and the ease by which consumers are purchasing non-deceptive counterfeits, should also not be ignored. Many retailers are now embracing ethical issues by emphasising, for example, that they take care of the production methods and working conditions pertaining to the goods they offer.

scholarly journals Generation and Activity Evaluation of a Mouse-Human Immunoglobulin G1 Chimeric Antibody to Histoplasma capsulatum HSP60

2021 ◽  
Author(s):  
Ágata Nogueira D'Áurea Moura ◽  
Scott J. Garforth ◽  
Leandro Buffoni Roque da Silva ◽  
Darien Woodley ◽  
Filipe Vieira Barbalho ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Histoplasma Capsulatum ◽  
Physiological Stress ◽  
Human Monoclonal Antibody ◽  
Current Treatment ◽  
Chimeric Antibody ◽  
Human Antibody ◽  
Chimeric Mouse ◽  
Dimorphic Fungi

Heat shock proteins (Hsps) are highly conserved molecules that are constitutively expressed and upregulated in response to physiological stress conditions. These immunogenic chaperones can have essential functions in fungi, particularly in dimorphic pathogens. Histoplasma capsulatum and Paracoccidioides species are dimorphic fungi that are the causative agents of histoplasmosis and paracoccidioidomycosis, respectively, which are systemic mycoses with significant rates of morbidity and mortality. Current treatment consists of long-term antifungal agents, and there is an urgent need for new therapeutic approaches with higher efficacy, lower toxicity, better biodistribution and improved selectivity. We engineered an immunoglobulin G1 (IgG1) isotype chimeric mouse-human monoclonal antibody, titled ch-MAb 4E12, from the parental IgG2a MAb 4E12, a monoclonal antibody to H. capsulatum Hsp60 that is protective in experimental histoplasmosis and paracoccidioidomycosis models elicited by H. capsulatum var. capsulatum and Paracoccidioides lutzii, respectively. The ch-MAb 4E12 increased phagolysosomal fusion and enhanced the yeasts uptake by PMA differentiated human THP1 macrophage cells in vitro. At low concentrations, the chimeric antibody significantly reduced the pulmonary and splenic fungal burden compared to an irrelevant antibody or no treatment. These results are the first to show that a chimeric mouse-human antibody can modify infection caused by dimorphic fungi.

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