Identification of Candida albicans regulatory genes governing mucosal infection
| Autor: | Andreas Rosenwald, Elena Hartmann, J. Christian Pérez, Marie-Therese Eckstein, Juliane Meir, Salomé LeibundGut-Landmann, Florian R. Kirchner, Eva Guiducci |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
030106 microbiology Immunology Biology Microbiology Oropharyngeal Candidiasis 03 medical and health sciences Immune system Candidiasis Oral Virology Candida albicans Genes Regulator Cell Adhesion Animals Genetic Testing Candidiasis Vulvovaginal Regulator gene Mice Inbred BALB C Mucous Membrane Virulence Effector Epithelial Cells biology.organism_classification Corpus albicans 3. Good health Mucosal Infection Colonisation Mice Inbred C57BL Disease Models Animal 030104 developmental biology Host-Pathogen Interactions Vagina Female Gene Deletion Transcription Factors |
| Zdroj: | Cellular microbiology. 20(8) |
| ISSN: | 1462-5822 |
| Popis: | The fungus Candida albicans thrives on a variety of human mucosae, yet the fungal determinants that contribute to fitness on these surfaces remain underexplored. Here, by screening a collection of C. albicans deletion strains in a mouse model of oral infection (oropharyngeal candidiasis), we identify several novel regulatory genes that modulate the fitness of the fungus in this locale. We investigate in detail the interplay between the host mucosa and one of the identified mutants and establish that the C. albicans transcription regulator CUP9 is a key determinant of mucosal colonisation. Deletion of cup9 resulted in the formation of more foci of colonisation and heightened persistence in infected tongues. Furthermore, the cup9 mutant produced longer and denser filaments in the oral mucosa without eliciting an enhanced local immune response. Consistent with its role in oral colonisation, we show that CUP9's top target of regulation is a major effector of Candida's adherence to buccal cells. Finally, we establish that CUP9 also governs the interplay of the fungus with vaginal epithelial cells and has a role in vaginal infections, another common mucosal disease associated with Candida. Thus, our findings reveal a mechanism whereby C. albicans can regulate proliferation on mucosal surfaces. |
| Databáze: | OpenAIRE |
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