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  1. Article ; 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  Volume 121, Issue 4, Page(s) 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 term(s) Animals ; Humans ; Candida albicans/genetics ; Transcription Factors/metabolism ; Regulatory Factor X1 ; Fungal Proteins/metabolism ; Mouth Mucosa/metabolism ; Epithelium/metabolism
    Chemical Substances Transcription Factors ; Regulatory Factor X1 ; Fungal Proteins ; RFX1 protein, human
    Language English
    Publishing date 2024-01-06
    Publishing country England
    Document type Journal Article
    ZDB-ID 619315-8
    ISSN 1365-2958 ; 0950-382X
    ISSN (online) 1365-2958
    ISSN 0950-382X
    DOI 10.1111/mmi.15219
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; 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  Volume 19, Issue 9, Page(s) 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 term(s) Animals ; Mice ; Humans ; Candida albicans ; Reactive Oxygen Species/metabolism ; Neutrophils/metabolism ; Candida ; Oxidants/metabolism ; Fungal Proteins/genetics ; Fungal Proteins/metabolism ; Mammals
    Chemical Substances Reactive Oxygen Species ; Oxidants ; Fungal Proteins
    Language English
    Publishing date 2023-09-28
    Publishing country United States
    Document type 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
    Database MEDical Literature Analysis and Retrieval System OnLINE

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