Center of Laboratory Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, China; Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, Shandong, 250033, China.
Center of Laboratory Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, China.
Microb Pathog. 2020 Nov;148:104451. doi: 10.1016/j.micpath.2020.104451. Epub 2020 Aug 14.
Acinetobacter baumannii (A. baumannii) is a common opportunistic nosocomial pathogen, which is able to produce biofilms on the surface of indwelling medical devices, and consequentially causes severe infections in clinical settings. In order to identify genes that involved in the biofilm formation of A. baumannii, the differential expression of genes between biofilms and planktonic cells was analyzed by RNAseq assay and validated in clinical isolates. The RNAseq data showed that 264 genes were up-regulated, while 240 genes were down-regulated in the biofilms of A. baumannii. Among them, the gene encoding alcohol dehydrogenase (ADH), a known molecule of bacterial quorum sensing (QS) system that plays a key role in biofilm formation bacteria, was one of the most up-regulated gene in both reference strains and clinical isolates. Functional studies using ADH inhibitor disulfiram and activator taurine further demonstrated that the presence of disulfiram significantly inhibit the cell growth, motility and biofilm formation, paralleled by a decreased expression of QS-related genes, including AbaI, A1S_0109, and A1S_0112, in a dose-dependent manner; vice versa, the addition of ADH activator taurine, and QS molecule C12- homoserine lactone synthase (HSL) led a dose-dependent increase of bacterial growth, motility and biofilm production, along with an increased expression of QS-related genes in both reference strains and clinical isolates of A. baumannii. These results suggested that the ADH was a key molecule able to modulate the QS system and promote the biofilm formation, growth and motility in A. baumannii.
鲍曼不动杆菌（A.baumannii）是一种常见的机会性医院获得性病原体，能够在留置医疗器械的表面形成生物膜，从而在临床环境中引起严重感染。为了鉴定参与鲍曼不动杆菌生物膜形成的基因，通过 RNAseq 分析和临床分离株验证分析了生物膜和浮游细胞之间基因的差异表达。RNAseq 数据显示，264 个基因上调，而 240 个基因下调。其中，编码醇脱氢酶（ADH）的基因是 A.baumannii 生物膜中上调最明显的基因之一，ADH 是细菌群体感应（QS）系统的已知分子，在细菌生物膜形成中起关键作用。使用 ADH 抑制剂二硫化四乙秋兰姆和激活剂牛磺酸的功能研究进一步表明，二硫化四乙秋兰姆的存在显著抑制细胞生长、运动和生物膜形成，同时 QS 相关基因的表达下调，包括 AbaI、A1S_0109 和 A1S_0112，呈剂量依赖性；反之，ADH 激活剂牛磺酸和 QS 分子 C12-高丝氨酸内酯合酶（HSL）的添加导致细菌生长、运动和生物膜形成呈剂量依赖性增加，同时 A.baumannii 参考株和临床分离株的 QS 相关基因表达增加。这些结果表明，ADH 是一种能够调节 QS 系统并促进鲍曼不动杆菌生物膜形成、生长和运动的关键分子。
