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  1. Artikel ; Online: RFX transcription factor in the human-associated yeast Candida albicans regulates adhesion to oral epithelium.

    Rodríguez, Diana L / Lindemann-Perez, Elena / Perez, J Christian

    Molecular microbiology

    2024  Band 121, Heft 4, Seite(n) 727–741

    Abstract: Adhesion to mucosal surfaces is a critical step in many bacterial and fungal infections. Here, using a mouse model of oral infection by the human fungal pathobiont Candida albicans, we report the identification of a novel regulator of C. albicans ... ...

    Abstract Adhesion to mucosal surfaces is a critical step in many bacterial and fungal infections. Here, using a mouse model of oral infection by the human fungal pathobiont Candida albicans, we report the identification of a novel regulator of C. albicans adhesion to the oral mucosa. The regulator is a member of the regulatory factor X (RFX) family of transcription factors, which control cellular processes ranging from genome integrity in model yeasts to tissue differentiation in vertebrates. Mice infected with the C. albicans rfx1 deletion mutant displayed increased fungal burden in tongues compared to animals infected with the reference strain. High-resolution imaging revealed RFX1 transcripts being expressed by C. albicans cells during infection. Concomitant with the increase in fungal burden, the rfx1 mutant elicited an enhanced innate immune response. Transcriptome analyses uncovered HWP1, a gene encoding an adhesion protein that mediates covalent attachment to buccal cells, as a major RFX1-regulated locus. Consistent with this result, we establish that C. albicans adhesion to oral cells is modulated by RFX1 in an HWP1-dependent manner. Our findings expand the repertoire of biological processes controlled by the RFX family and illustrate a mechanism whereby C. albicans can adjust adhesion to the oral epithelium.
    Mesh-Begriff(e) Animals ; Humans ; Candida albicans/genetics ; Epithelium/microbiology ; Fungal Proteins/genetics ; Fungal Proteins/metabolism ; Mouth Mucosa/microbiology ; Regulatory Factor X1/genetics ; Regulatory Factor X1/metabolism
    Sprache Englisch
    Erscheinungsdatum 2024-01-06
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 619315-8
    ISSN 1365-2958 ; 0950-382X
    ISSN (online) 1365-2958
    ISSN 0950-382X
    DOI 10.1111/mmi.15219
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Candida albicans natural diversity: a resource to dissect fungal commensalism and pathogenesis.

    Lindemann-Perez, Elena / Perez, J Christian

    Current opinion in microbiology

    2024  Band 80, Seite(n) 102493

    Abstract: Candida albicans is a ubiquitous fungus of humans. It is not only a component of the oral and intestinal microbiota of most healthy adults but also a major cause of mucosal disorders and life-threatening disseminated infections. Until recently, research ... ...

    Abstract Candida albicans is a ubiquitous fungus of humans. It is not only a component of the oral and intestinal microbiota of most healthy adults but also a major cause of mucosal disorders and life-threatening disseminated infections. Until recently, research on the biology and pathogenesis of the fungus was largely based on a single clinical isolate. We review investigations that have started to dissect a diverse set of C. albicans strains. Using different approaches to leverage the species' phenotypic and/or genetic diversity, these studies illuminate the wide range of interactions between fungus and host. While connecting genetic variants to phenotypes of interest remains challenging, research on C. albicans' natural diversity is central to understand fungal commensalism and pathogenesis.
    Sprache Englisch
    Erscheinungsdatum 2024-06-03
    Erscheinungsland England
    Dokumenttyp Journal Article ; Review
    ZDB-ID 1418474-6
    ISSN 1879-0364 ; 1369-5274
    ISSN (online) 1879-0364
    ISSN 1369-5274
    DOI 10.1016/j.mib.2024.102493
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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    Verfügbar in ZB MED Köln/Königswinter

    Zs.A 5514: Hefte anzeigen Standort:
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    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
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    ab Jg. 2022: Lesesaal (EG)
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  3. Artikel ; Online: Host-derived reactive oxygen species trigger activation of the Candida albicans transcription regulator Rtg1/3.

    Oneissi, Mazen / Cruz, Melissa R / Ramírez-Zavala, Bernardo / Lindemann-Perez, Elena / Morschhäuser, Joachim / Garsin, Danielle A / Perez, J Christian

    PLoS pathogens

    2023  Band 19, Heft 9, Seite(n) e1011692

    Abstract: The signals that denote mammalian host environments and dictate the activation of signaling pathways in human-associated microorganisms are often unknown. The transcription regulator Rtg1/3 in the human fungal pathogen Candida albicans is a crucial ... ...

    Abstract The signals that denote mammalian host environments and dictate the activation of signaling pathways in human-associated microorganisms are often unknown. The transcription regulator Rtg1/3 in the human fungal pathogen Candida albicans is a crucial determinant of host colonization and pathogenicity. Rtg1/3's activity is controlled, in part, by shuttling the regulator between the cytoplasm and nucleus of the fungus. The host signal(s) that Rtg1/3 respond(s) to, however, have remained unclear. Here we report that neutrophil-derived reactive oxygen species (ROS) direct the subcellular localization of this C. albicans transcription regulator. Upon engulfment of Candida cells by human or mouse neutrophils, the regulator shuttles to the fungal nucleus. Using genetic and chemical approaches to disrupt the neutrophils' oxidative burst, we establish that the oxidants produced by the NOX2 complex-but not the oxidants generated by myeloperoxidase-trigger Rtg1/3's migration to the nucleus. Furthermore, screening a collection of C. albicans kinase deletion mutants, we implicate the MKC1 signaling pathway in the ROS-dependent regulation of Rtg1/3 in this fungus. Finally, we show that Rtg1/3 contributes to C. albicans virulence in the nematode Caenorhabditis elegans in an ROS-dependent manner as the rtg1 and rtg3 mutants display virulence defects in wild-type but not in ROS deficient worms. Our findings establish NOX2-derived ROS as a key signal that directs the activity of the pleiotropic fungal regulator Rtg1/3.
    Mesh-Begriff(e) Animals ; Mice ; Humans ; Candida albicans ; Reactive Oxygen Species/metabolism ; Neutrophils/metabolism ; Candida ; Oxidants/metabolism ; Fungal Proteins/genetics ; Fungal Proteins/metabolism ; Mammals
    Chemische Substanzen Reactive Oxygen Species ; Oxidants ; Fungal Proteins
    Sprache Englisch
    Erscheinungsdatum 2023-09-28
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7374
    ISSN (online) 1553-7374
    ISSN 1553-7374
    DOI 10.1371/journal.ppat.1011692
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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