The Experts below are selected from a list of 21138 Experts worldwide ranked by ideXlab platform
Stephanie Diezmann - One of the best experts on this subject based on the ideXlab platform.
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tobacco hornworm manduca sexta caterpillars as a novel host model for the study of Fungal Virulence and drug efficacy
Virulence, 2020Co-Authors: Naomi Lyons, Isabel Softley, Andrew Balfour, Carolyn Williamson, Heath E Obrien, Stephanie Diezmann, Amol C Shetty, Vincent M BrunoAbstract:The two leading yeast pathogens of humans, Candida albicans and Cryptococcus neoformans, cause systemic infections in >1.4 million patients worldwide with mortality rates approaching 75%. It is thus imperative to study Fungal Virulence mechanisms, efficacy of antiFungal drugs, and host response pathways. While this is commonly done in mammalian models, which are afflicted by ethical and practical concerns, invertebrate models, such as wax moth larvae and nematodes have been introduced over the last two decades. To complement existing invertebrate host models, we developed fifth instar caterpillars of the Tobacco Hornworm moth Manduca sexta as a novel host model. These caterpillars can be maintained at 37°C, are suitable for injections with defined amounts of yeast cells, and are susceptible to the most threatening yeast pathogens, including C. albicans, C. neoformans, C. auris, and C. glabrata. Importantly, Fungal burden can be assessed daily throughout the course of infection in a single caterpillar's feces and hemolymph. Infected caterpillars can be rescued by treatment with antiFungal drugs. Notably, these animals are large enough for weight to provide a reliable and reproducible measure of Fungal disease and to facilitate host tissue-specific expression analyses. M. sexta caterpillars combine a suite of parameters that make them suitable for the study of Fungal Virulence.
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tobacco hornworm manduca sexta caterpillars as a novel host model for the study of Fungal Virulence and drug efficacy
bioRxiv, 2020Co-Authors: Naomi Lyons, Isabel Softley, Andrew Balfour, Carolyn Williamson, Heath E Obrien, Amol C Shetty, Vincent M Bruno, Stephanie DiezmannAbstract:The two leading yeast pathogens of humans, Candida albicans and Cryptococcus neoformans, cause systemic infections in >1.4 million patients world-wide with mortality rates approaching 75%. It is thus imperative to study Fungal Virulence mechanisms, efficacy of antiFungal drugs, and host response pathways. While this is commonly done in mammalian models, which are afflicted by ethical and practical concerns, invertebrate models, such as wax moth larvae and nematodes have been introduced over the last two decades. To complement existing invertebrate host models, we developed fifth instar caterpillars of the Tobacco Hornworm moth Manduca sexta as a novel host model. These caterpillars can be maintained at 37°C, are suitable for injections with defined amounts of yeast cells, and are susceptible to the most threatening yeast pathogens, including C. albicans, C. neoformans, C. auris, and C. glabrata. Importantly, Fungal burden can be assessed daily throughout the course of infection in a single caterpillars faeces and haemolymph. Infected caterpillars can be rescued by treatment with antiFungal drugs. Notably, these animals are large enough for weight to provide a reliable and reproducible measure of Fungal disease. M. sexta caterpillars combine a suite of parameters that make them suitable for the study of Fungal Virulence.
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the little caterpillar that could tobacco hornworm manduca sexta caterpillars as a novel host model for the study of Fungal Virulence and drug efficacy
bioRxiv, 2019Co-Authors: Naomi Lyons, Isabel Softley, Andrew Balfour, Carolyn Williamson, Heath E Obrien, Stephanie DiezmannAbstract:Abstract Pathogenic yeast species can cause life-threatening infections in humans. The two leading yeast pathogens, Candida albicans and Cryptococcus neoformans, cause systemic infections in >1.4 million patients world-wide with mortality rates approaching 75%. It is thus imperative to study Fungal Virulence mechanisms, stress response pathways, and the efficacy of antiFungal drugs. This is commonly done using mammalian models. To address ethical and practical concerns, invertebrate models, such as wax moth larvae, nematodes, or flies, have been introduced over the last two decades. To address short-comings in existing invertebrate host models, we developed fifth instar caterpillars of the Tobacco Hornworm moth Manduca sexta as a novel host model for the study of Fungal Virulence and drug efficacy. These caterpillars can be raised at standardised conditions, maintained at 37°C, can be injected with defined amounts of yeast cells, and are susceptible to the most threatening yeast pathogens, including C. albicans, C. neoformans, C. auris, and C. glabrata. Infected caterpillars can be rescued by treatment with commonly deployed antiFungal drugs and importantly, Fungal burden can be assessed daily throughout the course of infection in a single caterpillar’s faeces and hemolymph. Notably, these animals are large enough so that weight provides a reliable and reproducible measure of Fungal Virulence. This model combines a suite of parameters that recommend it for the study of Fungal Virulence.
Naomi Lyons - One of the best experts on this subject based on the ideXlab platform.
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tobacco hornworm manduca sexta caterpillars as a novel host model for the study of Fungal Virulence and drug efficacy
Virulence, 2020Co-Authors: Naomi Lyons, Isabel Softley, Andrew Balfour, Carolyn Williamson, Heath E Obrien, Stephanie Diezmann, Amol C Shetty, Vincent M BrunoAbstract:The two leading yeast pathogens of humans, Candida albicans and Cryptococcus neoformans, cause systemic infections in >1.4 million patients worldwide with mortality rates approaching 75%. It is thus imperative to study Fungal Virulence mechanisms, efficacy of antiFungal drugs, and host response pathways. While this is commonly done in mammalian models, which are afflicted by ethical and practical concerns, invertebrate models, such as wax moth larvae and nematodes have been introduced over the last two decades. To complement existing invertebrate host models, we developed fifth instar caterpillars of the Tobacco Hornworm moth Manduca sexta as a novel host model. These caterpillars can be maintained at 37°C, are suitable for injections with defined amounts of yeast cells, and are susceptible to the most threatening yeast pathogens, including C. albicans, C. neoformans, C. auris, and C. glabrata. Importantly, Fungal burden can be assessed daily throughout the course of infection in a single caterpillar's feces and hemolymph. Infected caterpillars can be rescued by treatment with antiFungal drugs. Notably, these animals are large enough for weight to provide a reliable and reproducible measure of Fungal disease and to facilitate host tissue-specific expression analyses. M. sexta caterpillars combine a suite of parameters that make them suitable for the study of Fungal Virulence.
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tobacco hornworm manduca sexta caterpillars as a novel host model for the study of Fungal Virulence and drug efficacy
bioRxiv, 2020Co-Authors: Naomi Lyons, Isabel Softley, Andrew Balfour, Carolyn Williamson, Heath E Obrien, Amol C Shetty, Vincent M Bruno, Stephanie DiezmannAbstract:The two leading yeast pathogens of humans, Candida albicans and Cryptococcus neoformans, cause systemic infections in >1.4 million patients world-wide with mortality rates approaching 75%. It is thus imperative to study Fungal Virulence mechanisms, efficacy of antiFungal drugs, and host response pathways. While this is commonly done in mammalian models, which are afflicted by ethical and practical concerns, invertebrate models, such as wax moth larvae and nematodes have been introduced over the last two decades. To complement existing invertebrate host models, we developed fifth instar caterpillars of the Tobacco Hornworm moth Manduca sexta as a novel host model. These caterpillars can be maintained at 37°C, are suitable for injections with defined amounts of yeast cells, and are susceptible to the most threatening yeast pathogens, including C. albicans, C. neoformans, C. auris, and C. glabrata. Importantly, Fungal burden can be assessed daily throughout the course of infection in a single caterpillars faeces and haemolymph. Infected caterpillars can be rescued by treatment with antiFungal drugs. Notably, these animals are large enough for weight to provide a reliable and reproducible measure of Fungal disease. M. sexta caterpillars combine a suite of parameters that make them suitable for the study of Fungal Virulence.
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the little caterpillar that could tobacco hornworm manduca sexta caterpillars as a novel host model for the study of Fungal Virulence and drug efficacy
bioRxiv, 2019Co-Authors: Naomi Lyons, Isabel Softley, Andrew Balfour, Carolyn Williamson, Heath E Obrien, Stephanie DiezmannAbstract:Abstract Pathogenic yeast species can cause life-threatening infections in humans. The two leading yeast pathogens, Candida albicans and Cryptococcus neoformans, cause systemic infections in >1.4 million patients world-wide with mortality rates approaching 75%. It is thus imperative to study Fungal Virulence mechanisms, stress response pathways, and the efficacy of antiFungal drugs. This is commonly done using mammalian models. To address ethical and practical concerns, invertebrate models, such as wax moth larvae, nematodes, or flies, have been introduced over the last two decades. To address short-comings in existing invertebrate host models, we developed fifth instar caterpillars of the Tobacco Hornworm moth Manduca sexta as a novel host model for the study of Fungal Virulence and drug efficacy. These caterpillars can be raised at standardised conditions, maintained at 37°C, can be injected with defined amounts of yeast cells, and are susceptible to the most threatening yeast pathogens, including C. albicans, C. neoformans, C. auris, and C. glabrata. Infected caterpillars can be rescued by treatment with commonly deployed antiFungal drugs and importantly, Fungal burden can be assessed daily throughout the course of infection in a single caterpillar’s faeces and hemolymph. Notably, these animals are large enough so that weight provides a reliable and reproducible measure of Fungal Virulence. This model combines a suite of parameters that recommend it for the study of Fungal Virulence.
Eleftherios Mylonakis - One of the best experts on this subject based on the ideXlab platform.
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caenorhabditis elegans a nematode infection model for pathogenic fungi
Methods of Molecular Biology, 2012Co-Authors: Maged Muhammed, Jeffrey J Coleman, Eleftherios MylonakisAbstract: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.
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methods for using galleria mellonella as a model host to study Fungal pathogenesis
Virulence, 2010Co-Authors: Beth Burgwyn Fuchs, Elizabeth Obrien, Joseph El Khoury, Eleftherios MylonakisAbstract: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.
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exploiting amoeboid and non vertebrate animal model systems to study the Virulence of human pathogenic fungi
PLOS Pathogens, 2007Co-Authors: Eleftherios Mylonakis, Arturo Casadevall, Frederick M AusubelAbstract: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.
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using non mammalian hosts to study Fungal Virulence and host defense
Current Opinion in Microbiology, 2006Co-Authors: Beth Burgwyn Fuchs, Eleftherios MylonakisAbstract: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.
Guoxiong Peng - One of the best experts on this subject based on the ideXlab platform.
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integration of an insecticidal scorpion toxin bjαit gene into metarhizium acridum enhances Fungal Virulence towards locusta migratoria manilensis
Pest Management Science, 2015Co-Authors: Guoxiong PengAbstract:BACKGROUND Entomopathogenic fungi have been developed as biopesticides, but poor efficacy has blocked their application. One approach to improving Virulence is by genetic manipulation. BjαIT from the venom of Buthotus judaicus is an insect-selective neurotoxin. To clarify the insecticidal potency of BjαIT as a Virulence candidate in microbial biocontrol agents, the entomopathogenic fungus Metarhizium acridum was genetically modified with BjαIT, and its resulting activity against locusts (Locusta migratoria manilensis) was assessed. RESULT In comparison with the wild-type strain, the engineered isolate BjαIT-102 grew significantly quicker in locust haemolymph. Correspondingly, the median lethal dose (LC50) for BjαIT-102 was 18.2-fold lower, and the median lethal times (LT50) for BjαIT-102 were reduced by 28.1 and 30.4%, respectively, after topical inoculation and injection. BjαIT-102 formed conidia on dead locusts, although the conidial yield was reduced 1.58-fold. Moreover, there were no significant differences in germination and appressorium formation between the BjαIT-102 and wild-type strains. CONCLUSION Expression of BjαIT in M. acridum significantly increased Virulence against locusts by shortening the in vivo infection period without affecting conidium formation on the carcasses. This study demonstrated that engineering entomopathogenic fungi to incorporate BjαIT offers great potential for increasing their Virulence. © 2014 Society of Chemical Industry
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expression of scorpion toxin lqhit2 increases the Virulence of metarhizium acridum towards locusta migratoria manilensis
Journal of Industrial Microbiology & Biotechnology, 2014Co-Authors: Guoxiong PengAbstract:LqhIT2 is an insect-specific neurotoxin from the venom of scorpion. In this study, the LqhIT2 gene was introduced into the entomopathogenic fungus, Metarhizium acridum. The Virulence of the genetically modified strain MaLqhIT2 was then evaluated against locusts (Locusta migratoria manilensis). Compared with the wild-type strain, the median lethal cell density (LC50) for MaLqhIT2 was a 22.6-fold lower, and the median times to death (LT50) for MaLqhIT2 were reduced by 30.3 and 29.6 %, respectively, after topical inoculation and injection. MaLqhIT2 also grew significantly faster in the hemolymph than wild-type strain. There were no significant differences in germination, appressorium formation and sporulation in locust carcasses between the MaLqhIT2 and wild-type strain. These results indicate that LqhIT2 increased the Virulence of M. acridum towards locusts by shortening the in vivo infection period, without affecting cuticle penetration or conidia formation in the carcasses. LqhIT2 thus shows considerable potential for increasing Fungal Virulence against locusts.
Chen Ding - One of the best experts on this subject based on the ideXlab platform.
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investigation of cryptococcus neoformans magnesium transporters reveals important role of vacuolar magnesium transporter in regulating Fungal Virulence factors
MicrobiologyOpen, 2018Co-Authors: Chenhao Suo, Jianfang Sun, Minghui Lin, Tianshu Sun, Xindi Gao, Yang Meng, Sixiang Sai, Chen DingAbstract:Cryptococcus neoformans is an important opportunistic Fungal pathogen in humans. Recent studies have demonstrated that metals are critical factors for the regulation of Fungal Virulence in hosts. In this study, we systemically investigated the function of C. neoformans magnesium transporters in controlling the intracellular Mg balance and Virulence-associated factors. We identified three Mg transporters in C. neoformans: Mgt1, Mgt2, and Mgt3. While we could not detect a Mg2+ -related growth phenotype in mgt1 and mgt3 knockout strains, a GAL7p-Mgt2 strain showed significant Mg-dependent growth defects in the presence of glucose. Further analysis demonstrated that MGT2 is a homolog of MNR2 in Saccharomyces cerevisiae, which is localized to the vacuolar membrane and participates in intracellular Mg transport. Interestingly, a transcriptome analysis showed that Mgt2 influenced the expression of 19 genes, which were independent of Mg2+ . We showed that melanin synthesis in C. neoformans required Mg2+ and Mgt2, and that capsule production was negatively regulated by Mg2+ and Mgt2. Repressing the expression of MGT2-induced capsule, which resulted in an increased Fungal burden in the lungs. Cumulatively, this study sets the stage for further evaluation of the important role of Mg homeostasis in the regulation of melanin and capsule in C. neoformans.
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reciprocal functions of cryptococcus neoformans copper homeostasis machinery during pulmonary infection and meningoencephalitis
Nature Communications, 2014Co-Authors: Tianshu Sun, Huiling Gao, Tao Wang, Dennis J Thiele, Zhanyou Wang, Chen DingAbstract:Copper homeostasis is important for Virulence of the fungus Cryptococcus neoformans, which can cause lethal meningoencephalitis in humans. Cryptococcus cells encounter high copper levels in the lung, where infection is initiated, and low copper levels in the brain. Here we demonstrate that two Cryptococcus copper transporters, Ctr1 and Ctr4, differentially influence Fungal survival during pulmonary infection and the onset of meningoencephalitis. Protein Ctr1 is rapidly degraded under the high-copper conditions found in infected lungs, and its loss has no effect in Fungal Virulence in mice. By contrast, deleting CTR4 results in a hypervirulent phenotype. Overexpressing either Ctr1 or Ctr4 leads to profound reductions in Fungal burden in the lung. However, during the onset of meningoencephalitis, expression of the copper transporters is induced and is critical for Cryptococcus Virulence. Our work demonstrates that the Fungal cells switch between copper detoxification and acquisition to address different copper stresses in the host.
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cryptococcus neoformans copper detoxification machinery is critical for Fungal Virulence
Cell Host & Microbe, 2013Co-Authors: Chen Ding, Joseph Heitman, Richard A Festa, Yinglien Chen, Anna Espart, Oscar Palacios, Jordi Espin, Merce Capdevila, Silvia Atrian, Dennis J ThieleAbstract:SUMMARY Copper (Cu) is an essential metal that is toxic at high concentrations. Thus, pathogens often rely on host Cu for growth, but host cells can hyperaccumulate Cu to exert antimicrobial effects. The human Fungal pathogen Cryptococcus neoformans encodes many Cu-responsive genes, but their role in infection is unclear. We determined that pulmonary C. neoformans infection results in Cu-specific induction of genes encoding the Cu-detoxifying metallothionein (Cmt) proteins. Mutant strains lacking CMTs or expressing Cmt variants defective in Cu-coordination exhibit severely attenuated Virulence and reduced pulmonary colonization. Consistent with the upregulation of Cmt proteins, C. neoformans pulmonary infection results in increased serum Cu concentrations and increases and decreases alveolar macrophage expression of the Cu importer (Ctr1) and ATP7A, a transporter implicated in phagosomal Cu compartmentalization, respectively. These studies indicate that the host mobilizes Cu as an innate antiFungal defense but C. neoformans senses and neutralizes toxic Cu to promote infection.
