The yeast form of the fungus Candida albicans promotes persistence in the gut of gnotobiotic mice

PLoS Pathogens

J. Christian Pérez¹  Sanda Torsin¹  Lena Böhm²  Marie Therese Eckstein²  Su Hlaing Tint²  Tobias Ludwig² 

[1] Institute for Molecular Infection Biology, University of Würzburg, Würzburg, Germany;Interdisciplinary Center for Clinical Research, University Hospital Würzburg, Würzburg, Germany

关键词: C;    ida albicans;    Gastrointestinal tract;    Fungi;    Regulator genes;    Deletion mutagenesis;    Gene regulation;    Mouse models;    Fungal genetics;   

DOI  :  10.1371/journal.ppat.1006699

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Many microorganisms that cause systemic, life-threatening infections in humans reside as harmless commensals in our digestive tract. Yet little is known about the biology of these microbes in the gut. Here, we visualize the interface between the human commensal and pathogenic fungus Candida albicans and the intestine of mice, a surrogate host. Because the indigenous mouse microbiota restricts C. albicans settlement, we compared the patterns of colonization in the gut of germ free and antibiotic-treated conventionally raised mice. In contrast to the heterogeneous morphologies found in the latter, we establish that in germ free animals the fungus almost uniformly adopts the yeast cell form, a proxy of its commensal state. By screening a collection of C. albicans transcription regulator deletion mutants in gnotobiotic mice, we identify several genes previously unknown to contribute to in vivo fitness. We investigate three of these regulators—ZCF8, ZFU2 and TRY4—and show that indeed they favor the yeast form over other morphologies. Consistent with this finding, we demonstrate that genetically inducing non-yeast cell morphologies is detrimental to the fitness of C. albicans in the gut. Furthermore, the identified regulators promote adherence of the fungus to a surface covered with mucin and to mucus-producing intestinal epithelial cells. In agreement with this result, histology sections indicate that C. albicans dwells in the murine gut in close proximity to the mucus layer. Thus, our findings reveal a set of regulators that endows C. albicans with the ability to endure in the intestine through multiple mechanisms.

【 授权许可】

CC BY