PDF(Pubmed)
Abstract：
Candida albicans is a commensal of the human microbiota that can form biofilms on implanted medical devices. These biofilms are tolerant to antifungals and to the host immune system. To identify novel genes modulating C. albicans biofilm formation, we performed a large-scale screen with 2,454 C. albicans doxycycline-dependent overexpression strains and identified 16 genes whose overexpression significantly hampered biofilm formation. Among those, overexpression of the ZCF15 and ZCF26 paralogs that encode transcription factors and have orthologs only in biofilm-forming species of the Candida clade, caused impaired biofilm formation both in vitro and in vivo. Interestingly, overexpression of ZCF15 impeded biofilm formation without any defect in hyphal growth. Transcript profiling, transcription factor binding, and phenotypic microarray analyses conducted upon overexpression of ZCF15 and ZCF26 demonstrated their role in reprogramming cellular metabolism by regulating central metabolism including glyoxylate and tricarboxylic acid cycle genes. Taken together, this study has identified a new set of biofilm regulators, including ZCF15 and ZCF26, that appear to control biofilm development through their specific role in metabolic remodeling.
摘要：
白色念珠菌是人类微生物群的共生菌，可以在植入的医疗设备上形成生物膜。这些生物膜耐受抗真菌剂和宿主免疫系统。鉴定调节白色念珠菌生物膜形成的新基因，我们对2,454个依赖多西环素的白色念珠菌过表达菌株进行了大规模筛选,鉴定出16个基因的过表达显著阻碍了生物膜的形成。其中,仅在念珠菌进化枝的生物膜形成物种中编码转录因子并具有直向同源物的ZCF15和ZCF26旁系同源物的过表达，导致体外和体内生物膜形成受损。有趣的是,ZCF15的过表达会阻碍生物膜的形成，而菌丝生长没有任何缺陷。成绩单分析，转录因子结合，和在ZCF15和ZCF26过表达时进行的表型微阵列分析证明了它们在通过调节包括乙醛酸和三羧酸循环基因在内的中枢代谢重编程细胞代谢中的作用。一起来看,这项研究确定了一套新的生物膜调节剂，包括ZCF15和ZCF26,其似乎通过其在代谢重塑中的特定作用来控制生物膜发育。
