A gain-of-function mutation in PDR1 of Candida glabrata decreases EPA1 expression and attenuates adherence to epithelial cells through enhancing recruitment of the Mediator subunit Gal11A
A gain-of-function mutation in PDR1 of Candida glabrata decreases EPA1 expression and attenuates adherence to epithelial cells through enhancing recruitment of the Mediator subunit Gal11A
复制标题
光滑念珠菌 PDR1 的功能获得性突变通过增强介质亚基 Gal11A 的募集来降低 EPA1 表达并减弱对上皮细胞的粘附
DOI：
10.1016/j.micres.2020.126519
复制
发表时间：
2020-10-01
影响因子：
6.7
通讯作者：
Guo，Lin
中科院分区：
文献类型：
--
作者：
Tian，Yuan;Zhuang，Yihui;Guo，Lin
Genetic studies have revealed critical roles of transcription factor Pdr1 and the Mediator subunit Gal11A in regulating azole resistance inCandida glabrata. Recently,PDR1gain-of-function (GOF) mutations have been shown to not only increase azole resistance but also enhance adherence duringC. glabratainfection. However, mechanism of how Pdr1 regulates adherence, especially the implication ofPDR1GOF mutations in the regulation of the major adhesin geneEPA1, remains uncharacterized. Initially, we unexpectedly observed that expression ofPDR1harbouring GOF mutation G346D down-regulatedEPA1transcription and attenuated adherence to epithelial cells in different strain backgrounds. Given thatPDR1GOF mutations have been previously regarded as stimulators for adherence of this species, these findings prompted us to explore the regulation ofEPA1by wild-type Pdr1 and Pdr1 harbouring G346D mutation. Epitope tagged version of Pdr1 and Gal11A were utilized to determine the association of Pdr1 and Gal11A withEPA1promoter. A combination of approaches including deletion, molecular, and biochemical assays showed thatEPA1is a direct target of Pdr1, and demonstrated for the first time thatPDR1G346D mutation decreasesEPA1expression and attenuates adherence to epithelial cells via enhancing recruitment of Gal11A. Taken together, our data propose a critical role of Gal11A in Pdr1-regulatedEPA1expression and adherence to epithelial cells, which could be utilized a novel therapeutic target for the treatment of hyper-adherentC. glabratainfection.
