Fungal Pathogenesis

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Eleftherios Mylonakis - One of the best experts on this subject based on the ideXlab platform.

  • selecting an invertebrate model host for the study of Fungal Pathogenesis
    PLOS Pathogens, 2012
    Co-Authors: Athanasios Desalermos, Beth Burgwyn Fuchs, Eleftherios Mylonakis
    Abstract:

    The authors have declared that no competing interests exist. This work was supported by the National Institutes of Health through an R01 award (AI075286) and an R21 award (AI070569) to EM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

  • caenorhabditis elegans a nematode infection model for pathogenic fungi
    Methods of Molecular Biology, 2012
    Co-Authors: Maged Muhammed, Jeffrey J Coleman, Eleftherios Mylonakis
    Abstract:

    Recent work suggests that Fungal virulence factors important in human disease have evolved through interactions with environmental predators such as amoebae, nematodes, and insects. This has allowed the use of simple model hosts for the study of Fungal Pathogenesis; specifically, the nematode Caenorhabditis elegans has become a model host to study medically important fungi. Alternative model hosts can be used as easy tools to identify virulence factors of pathogens, to study evolutionarily preserved immune responses, and to identify novel antiFungal compounds with low cost. This chapter describes assays utilizing the nematode in studies on Fungal-host interactions and antiFungal drug discovery. These assays include the nematode killing assay, the progeny permissive assay, and antiFungal compound discovery assay.

  • methods for using galleria mellonella as a model host to study Fungal Pathogenesis
    Virulence, 2010
    Co-Authors: Beth Burgwyn Fuchs, Elizabeth Obrien, Joseph El Khoury, Eleftherios Mylonakis
    Abstract:

    The facile inoculum delivery and handling of the insect Galleria mellonella make it a desirable model for the study of Fungal Pathogenesis. Here we present methods to study Fungal virulence, filamentation and Fungal cell associates with insect hemocytes using Candida albicans and Cryptococcus neoformans to illustrate the use of this model. The two types of fungi cause distinct infections thus we compare and contrast the infection characteristics observed in G. mellonella. The protocols presented herein can be adapted to the study of other Fungal pathogens using G. mellonella as an infection model.

  • exploiting amoeboid and non vertebrate animal model systems to study the virulence of human pathogenic fungi
    PLOS Pathogens, 2007
    Co-Authors: Eleftherios Mylonakis, Arturo Casadevall, Frederick M Ausubel
    Abstract:

    Experiments with insects, protozoa, nematodes, and slime molds have recently come to the forefront in the study of host–Fungal interactions. Many of the virulence factors required for pathogenicity in mammals are also important for Fungal survival during interactions with non-vertebrate hosts, suggesting that Fungal virulence may have evolved, and been maintained, as a countermeasure to environmental predation by amoebae and nematodes and other small non-vertebrates that feed on microorganisms. Host innate immune responses are also broadly conserved across many phyla. The study of the interaction between invertebrate model hosts and pathogenic fungi therefore provides insights into the mechanisms underlying pathogen virulence and host immunity, and complements the use of mammalian models by enabling whole-animal high throughput infection assays. This review aims to assist researchers in identifying appropriate invertebrate systems for the study of particular aspects of Fungal Pathogenesis.

  • using non mammalian hosts to study Fungal virulence and host defense
    Current Opinion in Microbiology, 2006
    Co-Authors: Beth Burgwyn Fuchs, Eleftherios Mylonakis
    Abstract:

    Non-mammalian hosts have been used to study host–Fungal interactions. Hosts such as Drosophila melanogaster, Caenorhabditis elegans, Acathamoeba castellanii, Dictyostelium discoideum, and Galleria mellonella have provided means to examine the physical barriers, cellular mechanisms and molecular elements of the host response. The Drosophila host-response to fungi is mediated through the Toll pathway, whereas in C. elegans the host-response is TIR-1-dependent. Virulence traits that are involved in mammalian infection are important for the interaction of fungi with these hosts. Screening of Fungal virulence traits using mutagenized fungi to determine changes in Fungal infectivity of non-mammalian hosts has been used to identify novel virulence proteins used to infect C. elegans such as Kin1 (a serine/threonine protein kinase) and Rom2 (a Rho1 guanyl-nucleotide exchange factor) from Cryptococcus neoformans. These heterologous non-mammalian hosts highlight the similarities and differences between different hosts in Fungal Pathogenesis and they complement studies in mammalian systems and those using other genetic approaches.

Arturo Casadevall - One of the best experts on this subject based on the ideXlab platform.

  • Fungal immunity and Pathogenesis in mammals versus the invertebrate model organism galleria mellonella
    Pathogens and Disease, 2021
    Co-Authors: Daniel F Q Smith, Arturo Casadevall
    Abstract:

    In recent decades, Galleria mellonella (Lepidoptera: Pyralidae) have emerged as a model system to explore experimental aspects of Fungal Pathogenesis. The benefits of the G. mellonella model include being faster, cheaper, higher-throughput, and easier compared to vertebrate models. Additionally, as invertebrates, their use is subject to fewer ethical and regulatory issues. However, for G. mellonella models to provide meaningful insight into Fungal Pathogenesis, the G. mellonella-Fungal interactions must be comparable to mammalian-Fungal interactions. Indeed, as discussed in the review, studies suggest that G. mellonella and mammalian immune systems share many similarities, and Fungal virulence factors show conserved functions in both hosts. While the moth model has opened novel research areas, many comparisons are superficial and leave large gaps of knowledge that need to be addressed concerning specific mechanisms underlying G. mellonella-Fungal interactions. Closing these gaps in understanding will strengthen G. mellonella as a model for Fungal virulence in the upcoming years. In this review we provide comprehensive comparisons between Fungal Pathogenesis in mammals and G. mellonellqa from immunological and virulence perspectives. When information on an antiFungal immune component is unknown in G. mellonella, we include findings from other well-studied Lepidoptera. We hope that by outlining this information available in related species we highlight areas of needed research and provide a framework for understanding G. mellonella immunity and Fungal interactions.

  • insights into Fungal Pathogenesis from the iatrogenic epidemic of exserohilum rostratum Fungal meningitis
    Fungal Genetics and Biology, 2013
    Co-Authors: David R Andes, Arturo Casadevall
    Abstract:

    In 2012 the medical community in the United States faced an unprecedented outbreak of Fungal meningitis caused by Exserohilum rostratum associated with injections of contaminated lots of methyprednilsone acetate. Rapid response by public health authorities led to the identification of the cause of the outbreak and the epidemic quickly abated, even though new cases were still being reported many months later. Although the cause of the outbreak is known there are many uncertainties regarding the management of infected individuals and the long term risk for those who were exposed to this organism. The epidemic of E. rostratum infections illustrates how an organism that normally has low pathogenic potential for humans can transform into a very dangerous pathogen when conditions are changed such that skin barriers are breached while it is simultaneously delivered with an immunosuppressive drug. Furthermore, this epidemic highlights the potential threats to human and animal health from the Fungal kingdom.

  • exploiting amoeboid and non vertebrate animal model systems to study the virulence of human pathogenic fungi
    PLOS Pathogens, 2007
    Co-Authors: Eleftherios Mylonakis, Arturo Casadevall, Frederick M Ausubel
    Abstract:

    Experiments with insects, protozoa, nematodes, and slime molds have recently come to the forefront in the study of host–Fungal interactions. Many of the virulence factors required for pathogenicity in mammals are also important for Fungal survival during interactions with non-vertebrate hosts, suggesting that Fungal virulence may have evolved, and been maintained, as a countermeasure to environmental predation by amoebae and nematodes and other small non-vertebrates that feed on microorganisms. Host innate immune responses are also broadly conserved across many phyla. The study of the interaction between invertebrate model hosts and pathogenic fungi therefore provides insights into the mechanisms underlying pathogen virulence and host immunity, and complements the use of mammalian models by enabling whole-animal high throughput infection assays. This review aims to assist researchers in identifying appropriate invertebrate systems for the study of particular aspects of Fungal Pathogenesis.

  • host as the variable model hosts approach the immunological asymptote
    Infection and Immunity, 2005
    Co-Authors: Arturo Casadevall
    Abstract:

    There is currently great interest in studying the interaction of nonmammalian hosts with microbes that are pathogenic to mammals. In recent years, numerous studies have reported the outcome of human pathogenic microbe interactions with such nonmammalian hosts as amoebae, slime molds, plants, worms, fish, and insects (18, 20, 24, 27, 32, 34). This trend is fueled by many forces, including the precedent established by the discovery of Toll receptors in flies (3), the realization that microbial virulence mechanisms are often shared and conserved among very different types of hosts (26), the suggestion that for certain microbes mammalian virulence may originate from interactions with nonmammalian hosts in the environment (7, 34), the attraction of simpler host-microbe systems with well-developed genetic tool boxes (32), fewer restrictions on the use of nonvertebrate hosts, and scientific curiosity about the extent to which host-microbe interactions are common. In this issue, we are presented with a timely Minireview on worms and flies as model hosts (20) and the description of yet another model host system for the study of Fungal Pathogenesis using moths (23). Clearly, the study of model hosts is a powerful tool in microbial Pathogenesis; yet, their use poses questions that range from the proper lexicon to the justification for this type of scientific inquiry.

Bernhard Hube - One of the best experts on this subject based on the ideXlab platform.

  • candidalysin discovery and function in candida albicans infections
    Current Opinion in Microbiology, 2019
    Co-Authors: Julian R Naglik, Sarah L Gaffen, Bernhard Hube
    Abstract:

    Candidalysin is a cytolytic peptide toxin secreted by the invasive form of the human pathogenic fungus, Candida albicans. Candidalysin is critical for mucosal and systemic infections and is a key driver of host cell activation, neutrophil recruitment and Type 17 immunity. Candidalysin is regarded as the first true classical virulence factor of C. albicans but also triggers protective immune responses. This review will discuss how candidalysin was discovered, the mechanisms by which this peptide toxin contributes to C. albicans infections, and how its discovery has advanced our understanding of Fungal Pathogenesis and disease.

  • metabolism in Fungal Pathogenesis
    Cold Spring Harbor Perspectives in Medicine, 2014
    Co-Authors: Sascha Brunke, Alistair J. P. Brown, Bernhard Hube
    Abstract:

    Fungal pathogens must assimilate local nutrients to establish an infection in their mammalian host. We focus on carbon, nitrogen, and micronutrient assimilation mechanisms, discussing how these influence host–fungus interactions during infection. We highlight several emerging trends based on the available data. First, the perturbation of carbon, nitrogen, or micronutrient assimilation attenuates Fungal pathogenicity. Second, the contrasting evolutionary pressures exerted on facultative versus obligatory pathogens have led to contemporary pathogenic Fungal species that display differing degrees of metabolic flexibility. The evolutionarily ancient metabolic pathways are conserved in most Fungal pathogen, but interesting gaps exist in some species (e.g., Candida glabrata). Third, metabolic flexibility is generally essential for Fungal pathogenicity, and in particular, for the adaptation to contrasting host microenvironments such as the gastrointestinal tract, mucosal surfaces, bloodstream, and internal organs. Fourth, this metabolic flexibility relies on complex regulatory networks, some of which are conserved across lineages, whereas others have undergone significant evolutionary rewiring. Fifth, metabolic adaptation affects Fungal susceptibility to antiFungal drugs and also presents exciting opportunities for the development of novel therapies.

  • embryonated chicken eggs as alternative infection model for pathogenic fungi
    Methods of Molecular Biology, 2012
    Co-Authors: Ilse D Jacobsen, Katharina Grosse, Bernhard Hube
    Abstract:

    Embryonated eggs have been used as infection models for decades in virology and bacteriology. However, they can also be used as an attractive alternative infection model for studying Fungal Pathogenesis. Here, we discuss some general aspects which need to be considered when working with embryonated eggs as infection models. Furthermore, we provide detailed protocols and technical tips for infection of embryonated eggs with Aspergillus fumigatus and Candida albicans via the chorioallantois membrane, as well as sampling methods for downstream analyses.

R A Dean - One of the best experts on this subject based on the ideXlab platform.

  • The genome sequence of the rice blast fungus Magnaporthe grisea
    Nature, 2005
    Co-Authors: R A Dean
    Abstract:

    Magnaporthe grisea is the most destructive pathogen of rice worldwide and the principal model organism for elucidating themolecular basis of Fungal disease of plants. Here, we report the draft sequence of the M. grisea genome. Analysis of the gene setprovides an insight into the adaptations required by a fungus to cause disease. The genome encodes a large and diverse set ofsecreted proteins, including those defined by unusual carbohydrate-binding domains. This fungus also possesses an expandedfamily of G-protein-coupled receptors, several new virulence-associated genes and large suites of enzymes involved in secondarymetabolism. Consistent with a role in Fungal Pathogenesis, the expression of several of these genes is upregulated during the earlystages of infection-related development. The M. grisea genome has been subject to invasion and proliferation of activetransposable elements, reflecting the clonal nature of this fungus imposed by widespread rice cultivation.

Beth Burgwyn Fuchs - One of the best experts on this subject based on the ideXlab platform.

  • selecting an invertebrate model host for the study of Fungal Pathogenesis
    PLOS Pathogens, 2012
    Co-Authors: Athanasios Desalermos, Beth Burgwyn Fuchs, Eleftherios Mylonakis
    Abstract:

    The authors have declared that no competing interests exist. This work was supported by the National Institutes of Health through an R01 award (AI075286) and an R21 award (AI070569) to EM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

  • methods for using galleria mellonella as a model host to study Fungal Pathogenesis
    Virulence, 2010
    Co-Authors: Beth Burgwyn Fuchs, Elizabeth Obrien, Joseph El Khoury, Eleftherios Mylonakis
    Abstract:

    The facile inoculum delivery and handling of the insect Galleria mellonella make it a desirable model for the study of Fungal Pathogenesis. Here we present methods to study Fungal virulence, filamentation and Fungal cell associates with insect hemocytes using Candida albicans and Cryptococcus neoformans to illustrate the use of this model. The two types of fungi cause distinct infections thus we compare and contrast the infection characteristics observed in G. mellonella. The protocols presented herein can be adapted to the study of other Fungal pathogens using G. mellonella as an infection model.

  • using non mammalian hosts to study Fungal virulence and host defense
    Current Opinion in Microbiology, 2006
    Co-Authors: Beth Burgwyn Fuchs, Eleftherios Mylonakis
    Abstract:

    Non-mammalian hosts have been used to study host–Fungal interactions. Hosts such as Drosophila melanogaster, Caenorhabditis elegans, Acathamoeba castellanii, Dictyostelium discoideum, and Galleria mellonella have provided means to examine the physical barriers, cellular mechanisms and molecular elements of the host response. The Drosophila host-response to fungi is mediated through the Toll pathway, whereas in C. elegans the host-response is TIR-1-dependent. Virulence traits that are involved in mammalian infection are important for the interaction of fungi with these hosts. Screening of Fungal virulence traits using mutagenized fungi to determine changes in Fungal infectivity of non-mammalian hosts has been used to identify novel virulence proteins used to infect C. elegans such as Kin1 (a serine/threonine protein kinase) and Rom2 (a Rho1 guanyl-nucleotide exchange factor) from Cryptococcus neoformans. These heterologous non-mammalian hosts highlight the similarities and differences between different hosts in Fungal Pathogenesis and they complement studies in mammalian systems and those using other genetic approaches.