Screening the Drug:H+ Antiporter Family for a Role in Biofilm Formation in Candida glabrata
Screening the Drug:H+ Antiporter Family for a Role in Biofilm Formation in Candida glabrata
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DOI：
10.3389/fcimb.2020.00029
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发表时间：
2020-02
影响因子：
5.7
通讯作者：
Rui Santos;Mafalda Cavalheiro;Catarina Costa;Azusa Takahashi-Nakaguchi;Michiyo Okamoto;H. Chibana;Miguel C. Teixeira
中科院分区：
文献类型：
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作者：
Rui Santos;Mafalda Cavalheiro;Catarina Costa;Azusa Takahashi-Nakaguchi;Michiyo Okamoto;H. Chibana;Miguel C. Teixeira
生物膜形成和耐药性是光滑念珠菌致病的两个重要特征。有趣的是，特定的途径似乎处于这两种现象之间的十字路口，使它们成为药物开发的有希望的目标。本研究对C.筛选glabrata在生物膜形成中的作用。除了先前在该过程中确定的参与者，即CgTpo1_2和CgQdr2之外，还显示了另外两个参与生物膜形成的参与者：CgDtr1和CgTpo4。这些基因中的每一个的缺失被发现导致较低的生物膜形成，在SDB和RPMI介质中，而它们的表达被发现在生物膜发育过程中增加，并被控制的转录因子CgTec1，预测的生物膜形成的关键调节。此外，发现CgDTR 1、CgTPO 4或甚至CgQDR 2的缺失增加质膜电位并导致生物膜形成期间粘附素编码基因（特别是CgALS 1和CgEPA1）的表达降低。虽然这些药物转运蛋白在生物膜形成中的确切作用仍然难以捉摸，但我们目前的模型表明，它们通过转运带电分子对膜电位的控制可能会影响对营养物质可用性的感知，这反过来可能会延迟粘附和生物膜形成的触发。
Biofilm formation and drug resistance are two key pathogenesis traits exhibited by Candida glabrata as a human pathogen. Interestingly, specific pathways appear to be in the crossroad between the two phenomena, making them promising targets for drug development. In this study, the 10 multidrug resistance transporters of the Drug:H+ Antiporter family of C. glabrata were screened for a role in biofilm formation. Besides previously identified players in this process, namely CgTpo1_2 and CgQdr2, two others are shown to contribute to biofilm formation: CgDtr1 and CgTpo4. The deletion of each of these genes was found to lead to lower biofilm formation, in both SDB and RPMI media, while their expression was found to increase during biofilm development and to be controlled by the transcription factor CgTec1, a predicted key regulator of biofilm formation. Additionally, the deletion of CgDTR1, CgTPO4, or even CgQDR2 was found to increase plasma membrane potential and lead to decreased expression of adhesin encoding genes, particularly CgALS1 and CgEPA1, during biofilm formation. Although the exact role of these drug transporters in biofilm formation remains elusive, our current model suggests that their control over membrane potential by the transport of charged molecules, may affect the perception of nutrient availability, which in turn may delay the triggering of adhesion and biofilm formation.