Interdisciplinary Center for Clinical Research, University Hospital Würzburg, Würzburg, Germany.
Institute for Molecular Infection Biology, University Würzburg, Würzburg, Germany.
Cell Microbiol. 2018 Aug;20(8):e12841. doi: 10.1111/cmi.12841. Epub 2018 Apr 18.
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.
白色念珠菌能在人体的多种黏膜上繁衍生息，然而，促进其在这些表面定植的真菌决定因素仍未得到充分探索。在这里，我们通过在口腔感染（口咽念珠菌病）的小鼠模型中筛选一系列白色念珠菌缺失株，鉴定出了几个新的调节基因，这些基因调节了真菌在该部位的适应性。我们详细研究了宿主黏膜与鉴定出的一个突变体之间的相互作用，证实了白色念珠菌转录调节因子 CUP9 是黏膜定植的关键决定因素。cup9 的缺失导致了更多的定植焦点和感染舌部的持续存在。此外，该突变体在口腔黏膜中产生了更长、更密集的菌丝，而没有引起增强的局部免疫反应。与它在口腔定植中的作用一致，我们表明 CUP9 的主要调控靶点是白色念珠菌黏附颊细胞的主要效应因子。最后，我们证实 CUP9 还控制着真菌与阴道上皮细胞的相互作用，并在阴道感染（另一种与白色念珠菌相关的常见黏膜疾病）中发挥作用。因此，我们的发现揭示了白色念珠菌可以调节在黏膜表面增殖的机制。
