Editorial

4 pages, 181 KiB

Open AccessEditorial

Current Status and Trends in Alternative Models to Study Fungal Pathogens

by Juliana Campos Junqueira and Eleftherios Mylonakis

J. Fungi 2019, 5(1), 12; https://doi.org/10.3390/jof5010012 - 26 Jan 2019

Cited by 3 | Viewed by 2793

Fungal infections affect over a billion people, with mortality rates estimated at 1–2 million per year [...] Full article

(This article belongs to the Special Issue Alternative Models for the Study of Fungal Host-Pathogen Interactions)

Research

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14 pages, 3241 KiB

Open AccessArticle

Anti-Candida albicans Activity of Thiazolylhydrazone Derivatives in Invertebrate and Murine Models

by Lana Ivone Barreto Cruz, Larissa Ferreira Finamore Lopes, Felipe De Camargo Ribeiro, Nívea Pereira De Sá, Cleudiomar Inácio Lino, Nagendran Tharmalingam, Renata Barbosa De Oliveira, Carlos Augusto Rosa, Eleftherios Mylonakis, Beth Burgwyn Fuchs and Susana Johann

J. Fungi 2018, 4(4), 134; https://doi.org/10.3390/jof4040134 - 12 Dec 2018

Cited by 15 | Viewed by 3823

Abstract

Candidiasis is an opportunistic fungal infection with Candida albicans being the most frequently isolated species. Treatment of these infections is challenging due to resistance that can develop during therapy, and the limited number of available antifungal compounds. Given this situation, the aim of [...] Read more.

Candidiasis is an opportunistic fungal infection with Candida albicans being the most frequently isolated species. Treatment of these infections is challenging due to resistance that can develop during therapy, and the limited number of available antifungal compounds. Given this situation, the aim of this study was to evaluate the antifungal activity of four thiazolylhydrazone compounds against C. albicans. Thiazolylhydrazone compounds 1, 2, 3, and 4 were found to exert antifungal activity, with MICs of 0.125–16.0 μg/mL against C. albicans. The toxicity of the compounds was evaluated using human erythrocytes and yielded LC₅₀ > 64 μg/mL. The compounds were further evaluated using the greater wax moth Galleria mellonella as an in vivo model. The compounds prolonged larval survival when tested between 5 and 15 mg/kg, performing as well as fluconazole. Compound 2 was evaluated in murine models of oral and systemic candidiasis. In the oral model, compound 2 reduced the fungal load on the mouse tongue; and in the systemic model it reduced the fungal burden found in the kidney when tested at 10 mg/kg. These results show that thiazolylhydrazones are an antifungal towards C. albicans with in vivo efficacy. Full article

(This article belongs to the Special Issue Alternative Models for the Study of Fungal Host-Pathogen Interactions)

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Review

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14 pages, 1395 KiB

Open AccessReview

The ‘Amoeboid Predator-Fungal Animal Virulence’ Hypothesis

by Arturo Casadevall, Man Shun Fu, Allan J. Guimaraes and Patricia Albuquerque

J. Fungi 2019, 5(1), 10; https://doi.org/10.3390/jof5010010 - 21 Jan 2019

Cited by 56 | Viewed by 7489

Abstract

The observation that some aspects of amoeba-fungal interactions resemble animal phagocytic cell-fungal interactions, together with the finding that amoeba passage can enhance the virulence of some pathogenic fungi, has stimulated interest in the amoeba as a model system for the study of fungal [...] Read more.

The observation that some aspects of amoeba-fungal interactions resemble animal phagocytic cell-fungal interactions, together with the finding that amoeba passage can enhance the virulence of some pathogenic fungi, has stimulated interest in the amoeba as a model system for the study of fungal virulence. Amoeba provide a relatively easy and cheap model system where multiple variables can be controlled for the study of fungi-protozoal (amoeba) interactions. Consequently, there have been significant efforts to study fungal–amoeba interactions in the laboratory, which have already provided new insights into the origin of fungal virulence as well as suggested new avenues for experimentation. In this essay we review the available literature, which highlights the varied nature of amoeba-fungal interactions and suggests some unsolved questions that are potential areas for future investigation. Overall, results from multiple independent groups support the ‘amoeboid predator–fungal animal virulence hypothesis’, which posits that fungal cell predation by amoeba can select for traits that also function during animal infection to promote their survival and thus contribute to virulence. Full article

(This article belongs to the Special Issue Alternative Models for the Study of Fungal Host-Pathogen Interactions)

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13 pages, 654 KiB

Open AccessReview

Immune Response of Galleria mellonella against Human Fungal Pathogens

by Nuria Trevijano-Contador and Oscar Zaragoza

J. Fungi 2019, 5(1), 3; https://doi.org/10.3390/jof5010003 - 26 Dec 2018

Cited by 75 | Viewed by 6687

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Alternative Models for the Study of Fungal Host-Pathogen Interactions)

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26 pages, 1270 KiB

Open AccessReview

The Zebrafish as a Model Host for Invasive Fungal Infections

by Emily E. Rosowski, Benjamin P. Knox, Linda S. Archambault, Anna Huttenlocher, Nancy P. Keller, Robert T. Wheeler and J. Muse Davis

J. Fungi 2018, 4(4), 136; https://doi.org/10.3390/jof4040136 - 13 Dec 2018

Cited by 42 | Viewed by 8851

Abstract

The zebrafish has become a widely accepted model host for studies of infectious disease, including fungal infections. The species is genetically tractable, and the larvae are transparent and amenable to prolonged in vivo imaging and small molecule screening. The aim of this review [...] Read more.

The zebrafish has become a widely accepted model host for studies of infectious disease, including fungal infections. The species is genetically tractable, and the larvae are transparent and amenable to prolonged in vivo imaging and small molecule screening. The aim of this review is to provide a thorough introduction into the published studies of fungal infection in the zebrafish and the specific ways in which this model has benefited the field. In doing so, we hope to provide potential new zebrafish researchers with a snapshot of the current toolbox and prior results, while illustrating how the model has been used well and where the unfulfilled potential of this model can be found. Full article

(This article belongs to the Special Issue Alternative Models for the Study of Fungal Host-Pathogen Interactions)

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19 pages, 1296 KiB

Open AccessReview

Recent Advances in the Use of Galleria mellonella Model to Study Immune Responses against Human Pathogens

by Thais Cristine Pereira, Patrícia Pimentel De Barros, Luciana Ruano de Oliveira Fugisaki, Rodnei Dennis Rossoni, Felipe de Camargo Ribeiro, Raquel Teles De Menezes, Juliana Campos Junqueira and Liliana Scorzoni

J. Fungi 2018, 4(4), 128; https://doi.org/10.3390/jof4040128 - 27 Nov 2018

Cited by 109 | Viewed by 8751

Abstract

The use of invertebrates for in vivo studies in microbiology is well established in the scientific community. Larvae of Galleria mellonella are a widely used model for studying pathogenesis, the efficacy of new antimicrobial compounds, and immune responses. The immune system of G. [...] Read more.

The use of invertebrates for in vivo studies in microbiology is well established in the scientific community. Larvae of Galleria mellonella are a widely used model for studying pathogenesis, the efficacy of new antimicrobial compounds, and immune responses. The immune system of G. mellonella larvae is structurally and functionally similar to the innate immune response of mammals, which makes this model suitable for such studies. In this review, cellular responses (hemocytes activity: phagocytosis, nodulation, and encapsulation) and humoral responses (reactions or soluble molecules released in the hemolymph as antimicrobial peptides, melanization, clotting, free radical production, and primary immunization) are discussed, highlighting the use of G. mellonella as a model of immune response to different human pathogenic microorganisms. Full article

(This article belongs to the Special Issue Alternative Models for the Study of Fungal Host-Pathogen Interactions)

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12 pages, 14782 KiB

Open AccessReview

An Invertebrate Host to Study Fungal Infections, Mycotoxins and Antifungal Drugs: Tenebrio molitor

by Patrícia Canteri de Souza, Carla Custódio Caloni, Duncan Wilson and Ricardo Sergio Almeida

J. Fungi 2018, 4(4), 125; https://doi.org/10.3390/jof4040125 - 12 Nov 2018

Cited by 27 | Viewed by 7775

Abstract

Faced with ethical conflict and social pressure, researchers have increasingly chosen to use alternative models over vertebrates in their research. Since the innate immune system is evolutionarily conserved in insects, the use of these animals in research is gaining ground. This review discusses [...] Read more.

Faced with ethical conflict and social pressure, researchers have increasingly chosen to use alternative models over vertebrates in their research. Since the innate immune system is evolutionarily conserved in insects, the use of these animals in research is gaining ground. This review discusses Tenebrio molitor as a potential model host for the study of pathogenic fungi. Larvae of T. molitor are known as cereal pests and, in addition, are widely used as animal and human feed. A number of studies on mechanisms of the humoral system, especially in the synthesis of antimicrobial peptides, which have similar characteristics to vertebrates, have been performed. These studies demonstrate the potential of T. molitor larvae as a model host that can be used to study fungal virulence, mycotoxin effects, host immune responses to fungal infection, and the action of antifungal compounds. Full article

(This article belongs to the Special Issue Alternative Models for the Study of Fungal Host-Pathogen Interactions)

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16 pages, 1265 KiB

Open AccessReview

Caenorhabditis elegans as a Model Host to Monitor the Candida Infection Processes

by Asmaa B. Elkabti, Luca Issi and Reeta P. Rao

J. Fungi 2018, 4(4), 123; https://doi.org/10.3390/jof4040123 - 07 Nov 2018

Cited by 30 | Viewed by 6035

Abstract

C. elegans has several advantages as an experimental host for the study of infectious diseases. Worms are easily maintained and propagated on bacterial lawns. The worms can be frozen for long term storage and still maintain viability years later. Their short generation time [...] Read more.

C. elegans has several advantages as an experimental host for the study of infectious diseases. Worms are easily maintained and propagated on bacterial lawns. The worms can be frozen for long term storage and still maintain viability years later. Their short generation time and large brood size of thousands of worms grown on a single petri dish, makes it relatively easy to maintain at a low cost. The typical wild type adult worm grows to approximately 1.5 mm in length and are transparent, allowing for the identification of several internal organs using an affordable dissecting microscope. A large collection of loss of function mutant strains are readily available from the C. elegans genetic stock center, making targeted genetic studies in the nematode possible. Here we describe ways in which this facile model host has been used to study Candida albicans, an opportunistic fungal pathogen that poses a serious public health threat. Full article

(This article belongs to the Special Issue Alternative Models for the Study of Fungal Host-Pathogen Interactions)

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19 pages, 1004 KiB

Open AccessReview

Applications of Invertebrate Animal Models to Dimorphic Fungal Infections

by Junya L. Singulani, Liliana Scorzoni, Haroldo C. De Oliveira, Caroline M. Marcos, Patricia A. Assato, Ana Marisa Fusco-Almeida and Maria José S. Mendes-Giannini

J. Fungi 2018, 4(4), 118; https://doi.org/10.3390/jof4040118 - 19 Oct 2018

Cited by 23 | Viewed by 5795

Abstract

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 [...] Read more.

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). Full article

(This article belongs to the Special Issue Alternative Models for the Study of Fungal Host-Pathogen Interactions)

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13 pages, 23547 KiB

Open AccessReview

The Use of Galleria mellonella Larvae to Identify Novel Antimicrobial Agents against Fungal Species of Medical Interest

by Kevin Kavanagh and Gerard Sheehan

J. Fungi 2018, 4(3), 113; https://doi.org/10.3390/jof4030113 - 19 Sep 2018

Cited by 60 | Viewed by 11100

Abstract

The immune system of insects and the innate immune response of mammals share many similarities and, as a result, insects may be used to assess the virulence of fungal pathogens and give results similar to those from mammals. Larvae of the greater wax [...] Read more.

The immune system of insects and the innate immune response of mammals share many similarities and, as a result, insects may be used to assess the virulence of fungal pathogens and give results similar to those from mammals. Larvae of the greater wax moth Galleria mellonella are widely used in this capacity and also for assessing the toxicity and in vivo efficacy of antifungal drugs. G. mellonella larvae are easy to use, inexpensive to purchase and house, and have none of the legal/ethical restrictions that are associated with use of mammals. Larvae may be inoculated by intra-hemocoel injection or by force-feeding. Larvae can be used to assess the in vivo toxicity of antifungal drugs using a variety of cellular, proteomic, and molecular techniques. Larvae have also been used to identify the optimum combinations of antifungal drugs for use in the treatment of recalcitrant fungal infections in mammals. The introduction of foreign material into the hemocoel of larvae can induce an immune priming effect which may operate independently with the activity of the antifungal drug. Procedures to identify this effect and limit its action are required. Full article

(This article belongs to the Special Issue Alternative Models for the Study of Fungal Host-Pathogen Interactions)

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11 pages, 549 KiB

Open AccessReview

Standardization of G. mellonella Larvae to Provide Reliable and Reproducible Results in the Study of Fungal Pathogens

by Olivia L. Champion, Richard W. Titball and Steven Bates

J. Fungi 2018, 4(3), 108; https://doi.org/10.3390/jof4030108 - 06 Sep 2018

Cited by 47 | Viewed by 6727

Abstract

In the past decade, Galleria mellonella (wax moth) larvae have become widely used as a non-mammalian infection model. However, the full potential of this infection model has yet to be realised, limited by the variable quality of larvae used and the lack of [...] Read more.

In the past decade, Galleria mellonella (wax moth) larvae have become widely used as a non-mammalian infection model. However, the full potential of this infection model has yet to be realised, limited by the variable quality of larvae used and the lack of standardised procedures. Here, we review larvae suitable for research, protocols for dosing larvae, and methods for scoring illness in larvae infected with fungal pathogens. The development of standardised protocols for carrying out our experimental work will allow high throughput screens to be developed, changing the way in which we evaluate panels of mutants and strains. It will also enable the in vivo screening of potential antimicrobials at an earlier stage in the research and development cycle. Full article

(This article belongs to the Special Issue Alternative Models for the Study of Fungal Host-Pathogen Interactions)

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