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  1. Article ; Online: Candida vaginitis: the importance of mitochondria and type I interferon signalling.

    Papon, Nicolas / Naglik, Julian R

    Mucosal immunology

    2021  Volume 14, Issue 5, Page(s) 975–977

    MeSH term(s) Biomarkers ; Candida/physiology ; Candidiasis, Vulvovaginal/diagnosis ; Candidiasis, Vulvovaginal/etiology ; Candidiasis, Vulvovaginal/metabolism ; Candidiasis, Vulvovaginal/therapy ; Disease Susceptibility ; Female ; Host-Pathogen Interactions/genetics ; Host-Pathogen Interactions/immunology ; Humans ; Interferon Type I/genetics ; Interferon Type I/metabolism ; Mitochondria/genetics ; Mitochondria/metabolism ; Mucous Membrane/immunology ; Mucous Membrane/metabolism ; Mucous Membrane/microbiology ; Signal Transduction
    Chemical Substances Biomarkers ; Interferon Type I
    Language English
    Publishing date 2021-06-19
    Publishing country United States
    Document type Letter
    ZDB-ID 2411370-0
    ISSN 1935-3456 ; 1933-0219
    ISSN (online) 1935-3456
    ISSN 1933-0219
    DOI 10.1038/s41385-021-00424-4
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  2. Article: EGR1 regulates oral epithelial cell responses to

    Dickenson, Ruth E / Pellon, Aize / Ponde, Nicole O / Hepworth, Olivia / Daniels Gatward, Lydia F / Naglik, Julian R / Moyes, David L

    bioRxiv : the preprint server for biology

    2023  

    Abstract: ... Candida ... ...

    Abstract Candida albicans
    Language English
    Publishing date 2023-04-03
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.03.31.535186
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Special Issue: Mucosal Fungal Infections.

    Richardson, Jonathan P / Naglik, Julian R

    Journal of fungi (Basel, Switzerland)

    2018  Volume 4, Issue 2

    Abstract: The past four decades have seen a staggering escalation in the number of invasive fungal infections worldwide.[ ... ]. ...

    Abstract The past four decades have seen a staggering escalation in the number of invasive fungal infections worldwide.[...].
    Language English
    Publishing date 2018-03-26
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2784229-0
    ISSN 2309-608X ; 2309-608X
    ISSN (online) 2309-608X
    ISSN 2309-608X
    DOI 10.3390/jof4020043
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  4. Article ; Online: Fungal pathogenesis: A new venom.

    Papon, Nicolas / Naglik, Julian R / Hube, Bernhard / Goldman, Gustavo H

    Current biology : CB

    2021  Volume 31, Issue 8, Page(s) R391–R394

    Abstract: The pathogenesis of life-threatening infections caused by emerging fungal pathogens remains largely unexplored. A new study provides unprecedented evidence for the pivotal role of a new ricin-like protein toxin, named mucoricin, in causing organ necrosis ...

    Abstract The pathogenesis of life-threatening infections caused by emerging fungal pathogens remains largely unexplored. A new study provides unprecedented evidence for the pivotal role of a new ricin-like protein toxin, named mucoricin, in causing organ necrosis and mortality in Mucorales infections.
    MeSH term(s) Animals ; Humans ; Mice ; Mucorales/chemistry ; Mucorales/pathogenicity ; Mucormycosis/microbiology ; Mycotoxins ; Venoms
    Chemical Substances Mycotoxins ; Venoms ; mucoricin
    Language English
    Publishing date 2021-04-27
    Publishing country England
    Document type Journal Article
    ZDB-ID 1071731-6
    ISSN 1879-0445 ; 0960-9822
    ISSN (online) 1879-0445
    ISSN 0960-9822
    DOI 10.1016/j.cub.2021.03.015
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  5. Article: Fungal Toxins and Host Immune Responses.

    Brown, Rhys / Priest, Emily / Naglik, Julian R / Richardson, Jonathan P

    Frontiers in microbiology

    2021  Volume 12, Page(s) 643639

    Abstract: Fungi are ubiquitous organisms that thrive in diverse natural environments including soils, plants, animals, and the human body. In response to warmth, humidity, and moisture, certain fungi which grow on crops and harvested foodstuffs can produce ... ...

    Abstract Fungi are ubiquitous organisms that thrive in diverse natural environments including soils, plants, animals, and the human body. In response to warmth, humidity, and moisture, certain fungi which grow on crops and harvested foodstuffs can produce mycotoxins; secondary metabolites which when ingested have a deleterious impact on health. Ongoing research indicates that some mycotoxins and, more recently, peptide toxins are also produced during active fungal infection in humans and experimental models. A combination of innate and adaptive immune recognition allows the host to eliminate invading pathogens from the body. However, imbalances in immune homeostasis often facilitate microbial infection. Despite the wide-ranging effects of fungal toxins on health, our understanding of toxin-mediated modulation of immune responses is incomplete. This review will explore the current understanding of fungal toxins and how they contribute to the modulation of host immunity.
    Language English
    Publishing date 2021-04-13
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2587354-4
    ISSN 1664-302X
    ISSN 1664-302X
    DOI 10.3389/fmicb.2021.643639
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  6. Article ; Online: In Vitro Biophysical Characterization of Candidalysin: A Fungal Peptide Toxin.

    Lee, Sejeong / Kichik, Nessim / Hepworth, Olivia W / Richardson, Jonathan P / Naglik, Julian R

    Methods in molecular biology (Clifton, N.J.)

    2022  Volume 2542, Page(s) 163–176

    Abstract: In 2016, the first peptide toxin in any human fungal pathogen was identified. It was discovered in Candida albicans and was named candidalysin. Candidalysin is an amphipathic cationic peptide that damages cell membranes. Like most lytic peptides, ... ...

    Abstract In 2016, the first peptide toxin in any human fungal pathogen was identified. It was discovered in Candida albicans and was named candidalysin. Candidalysin is an amphipathic cationic peptide that damages cell membranes. Like most lytic peptides, candidalysin shows alpha-helical secondary structure. As the helicity and the membrane lytic activity of candidalysin are key factors for pathogenicity, here we describe in vitro approaches to monitor both its membrane-lytic function and the secondary structure. First, membrane permeabilization activity of candidalysin is measured in real time by direct electrical recording. Second, the secondary structure and helicity of candidalysin are determined by circular dichroism spectroscopy. These biophysical methods provide a means to characterize the activity and physical properties of candidalysin in vitro and will be useful in determining the structural and functional features of candidalysin and other similar cationic membrane-active peptides.
    MeSH term(s) Candida albicans/metabolism ; Circular Dichroism ; Fungal Proteins/metabolism ; Humans ; Mycotoxins/metabolism ; Peptides/metabolism ; Virulence
    Chemical Substances ECE1 protein, Candida albicans ; Fungal Proteins ; Mycotoxins ; Peptides
    Language English
    Publishing date 2022-08-25
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-2549-1_12
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  7. Article ; Online: Aspergillus fumigatus Drives Tissue Damage via Iterative Assaults upon Mucosal Integrity and Immune Homeostasis.

    Okaa, Uju Joy / Bertuzzi, Margherita / Fortune-Grant, Rachael / Thomson, Darren D / Moyes, David L / Naglik, Julian R / Bignell, Elaine

    Infection and immunity

    2023  Volume 91, Issue 2, Page(s) e0033322

    Abstract: The human lung is constantly exposed to Aspergillus fumigatus spores, the most prevalent worldwide cause of fungal respiratory disease. Pulmonary tissue damage is a unifying feature of Aspergillus-related diseases; however, the mechanistic basis of ... ...

    Abstract The human lung is constantly exposed to Aspergillus fumigatus spores, the most prevalent worldwide cause of fungal respiratory disease. Pulmonary tissue damage is a unifying feature of Aspergillus-related diseases; however, the mechanistic basis of damage is not understood. In the lungs of susceptible hosts, A. fumigatus undergoes an obligatory morphological switch involving spore germination and hyphal growth. We modeled A. fumigatus infection in cultured A549 human pneumocytes, capturing the phosphoactivation status of five host signaling pathways, nuclear translocation and DNA binding of eight host transcription factors, and expression of nine host response proteins over six time points encompassing exposures to live fungus and the secretome thereof. The resulting data set, comprised of more than 1,000 data points, reveals that pneumocytes mount differential responses to A. fumigatus spores, hyphae, and soluble secreted products via the NF-κB, JNK, and JNK + p38 pathways, respectively. Importantly, via selective degradation of host proinflammatory (IL-6 and IL-8) cytokines and growth factors (FGF-2), fungal secreted products reorchestrate the host response to fungal challenge as well as driving multiparameter epithelial damage, culminating in cytolysis. Dysregulation of NF-κB signaling, involving sequential stimulation of canonical and noncanonical signaling, was identified as a significant feature of host damage both in vitro and in a mouse model of invasive aspergillosis. Our data demonstrate that composite tissue damage results from iterative (repeated) exposures to different fungal morphotypes and secreted products and suggest that modulation of host responses to fungal challenge might represent a unified strategy for therapeutic control of pathologically distinct types of Aspergillus-related disease.
    MeSH term(s) Animals ; Mice ; Humans ; Aspergillus fumigatus ; NF-kappa B/metabolism ; Aspergillosis ; Lung/microbiology ; Homeostasis ; Spores, Fungal
    Chemical Substances NF-kappa B
    Language English
    Publishing date 2023-01-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218698-6
    ISSN 1098-5522 ; 0019-9567
    ISSN (online) 1098-5522
    ISSN 0019-9567
    DOI 10.1128/iai.00333-22
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    Zs.A 684: Show issues Location:
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  8. Article ; Online: Immunity to pathogenic mucosal C. albicans infections mediated by oral megakaryocytes activated by IL-17 and candidalysin.

    Launder, Dylan / Dillon, John T / Wuescher, Leah M / Glanz, Trevor / Abdul-Aziz, Nora / Yi, Elise Mein-Chiain / Naglik, Julian R / Worth, Randall G / Conti, Heather R

    Mucosal immunology

    2024  Volume 17, Issue 2, Page(s) 182–200

    Abstract: The fungus Candida albicans can cause mucosal infections including oropharyngeal candidiasis (OPC) in immunocompromised patients. In humans, an increased risk of fungal infections correlates with thrombocytopenia. However, our understanding of platelets ... ...

    Abstract The fungus Candida albicans can cause mucosal infections including oropharyngeal candidiasis (OPC) in immunocompromised patients. In humans, an increased risk of fungal infections correlates with thrombocytopenia. However, our understanding of platelets and megakaryocytes (Mks) in mucosal fungal infections is almost entirely unknown. When megakaryocyte- and platelet-depleted mice were infected with OPC, the tongue showed higher fungal burden, due to decreased neutrophil accumulation. Protection depended on a distinct population of oral-resident Mks. Interleukin-17, important in antifungal immunity, was required since mice lacking the IL-17 receptor had decreased circulating platelets and their oral Mks did not expand during OPC. The secretion of the peptide toxin candidalysin activated human Mks to release platelets with antifungal capacity. Infection with a candidalysin-deficient strain resulted in decreased expansion of tongue Mks during OPC. This is the first time that a distinct megakaryocyte population was identified in the oral mucosa which is critical for immunity against fungal infection.
    MeSH term(s) Humans ; Mice ; Animals ; Candida albicans ; Megakaryocytes ; Interleukin-17 ; Antifungal Agents ; Candidiasis, Oral/microbiology ; Mouth Mucosa ; Communicable Diseases ; Mycoses ; Fungal Proteins
    Chemical Substances ECE1 protein, Candida albicans ; Interleukin-17 ; Antifungal Agents ; Fungal Proteins
    Language English
    Publishing date 2024-01-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2411370-0
    ISSN 1935-3456 ; 1933-0219
    ISSN (online) 1935-3456
    ISSN 1933-0219
    DOI 10.1016/j.mucimm.2024.01.003
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  9. Article ; Online: Candida albicans translocation through the intestinal epithelial barrier is promoted by fungal zinc acquisition and limited by NFκB-mediated barrier protection.

    Sprague, Jakob L / Schille, Tim B / Allert, Stefanie / Trümper, Verena / Lier, Adrian / Großmann, Peter / Priest, Emily L / Tsavou, Antzela / Panagiotou, Gianni / Naglik, Julian R / Wilson, Duncan / Schäuble, Sascha / Kasper, Lydia / Hube, Bernhard

    PLoS pathogens

    2024  Volume 20, Issue 3, Page(s) e1012031

    Abstract: The opportunistic fungal pathogen Candida albicans thrives on human mucosal surfaces as a harmless commensal, but frequently causes infections under certain predisposing conditions. Translocation across the intestinal barrier into the bloodstream by ... ...

    Abstract The opportunistic fungal pathogen Candida albicans thrives on human mucosal surfaces as a harmless commensal, but frequently causes infections under certain predisposing conditions. Translocation across the intestinal barrier into the bloodstream by intestine-colonizing C. albicans cells serves as the main source of disseminated candidiasis. However, the host and microbial mechanisms behind this process remain unclear. In this study we identified fungal and host factors specifically involved in infection of intestinal epithelial cells (IECs) using dual-RNA sequencing. Our data suggest that host-cell damage mediated by the peptide toxin candidalysin-encoding gene ECE1 facilitates fungal zinc acquisition. This in turn is crucial for the full virulence potential of C. albicans during infection. IECs in turn exhibit a filamentation- and damage-specific response to C. albicans infection, including NFκB, MAPK, and TNF signaling. NFκB activation by IECs limits candidalysin-mediated host-cell damage and mediates maintenance of the intestinal barrier and cell-cell junctions to further restrict fungal translocation. This is the first study to show that candidalysin-mediated damage is necessary for C. albicans nutrient acquisition during infection and to explain how IECs counteract damage and limit fungal translocation via NFκB-mediated maintenance of the intestinal barrier.
    MeSH term(s) Humans ; Candida albicans ; Zinc ; Candidiasis ; Epithelial Cells ; Intestines
    Chemical Substances Zinc (J41CSQ7QDS)
    Language English
    Publishing date 2024-03-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7374
    ISSN (online) 1553-7374
    ISSN 1553-7374
    DOI 10.1371/journal.ppat.1012031
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  10. Article ; Online: Candida albicans

    Ponde, Nicole O / Lortal, Léa / Ramage, Gordon / Naglik, Julian R / Richardson, Jonathan P

    Critical reviews in microbiology

    2021  Volume 47, Issue 1, Page(s) 91–111

    Abstract: ... Candida ... ...

    Abstract Candida albicans
    MeSH term(s) Animals ; Antifungal Agents/pharmacology ; Biofilms ; Candida albicans/drug effects ; Candida albicans/genetics ; Candida albicans/physiology ; Candidiasis/drug therapy ; Candidiasis/microbiology ; Fungal Proteins/genetics ; Fungal Proteins/metabolism ; Humans ; Virulence Factors/genetics ; Virulence Factors/metabolism
    Chemical Substances Antifungal Agents ; Fungal Proteins ; Virulence Factors
    Language English
    Publishing date 2021-01-22
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1053620-6
    ISSN 1549-7828 ; 1040-841X
    ISSN (online) 1549-7828
    ISSN 1040-841X
    DOI 10.1080/1040841X.2020.1843400
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