P. aeruginosa TY1-PA3898 ChIP-seq

We present here a transcriptional regulator, PA3898, which controls biofilm formation and multidrug efflux-pumps in P. aeruginosa. A mutant of this regulator significantly reduced the ability of P. aeruginosa to produce biofilm in vitro, and affected its in vivo fitness and pathogenesis in Drosophila melanogaster and BALB/c mouse lung infection models. Transcriptome analysis revealed that PA3898 modulates essential virulence genes/pathways, including multidrug efflux-pumps and phenazine biosynthesis.ChIP-seq identified its DNA binding sequences and confirmed PA3898 directly interacts with promoter regions of four genes/operons, two of which are mexAB-oprM and phz2. PAO1 strain contains TY1-tagged PA3898 was used to identify DNA sequences that interact with regulator via ChIP-seq

本研究报道了一种转录调控因子PA3898，其可调控铜绿假单胞菌（Pseudomonas aeruginosa，简称P. aeruginosa）的生物被膜形成与多药外排泵系统。该调控因子的突变体可显著降低铜绿假单胞菌的体外生物被膜形成能力，并影响其在黑腹果蝇（Drosophila melanogaster）与BALB/c小鼠肺部感染模型中的体内适合度与致病力。转录组学分析显示，PA3898可调控包括多药外排泵与吩嗪生物合成在内的关键毒力基因与通路。染色质免疫共沉淀测序（Chromatin Immunoprecipitation sequencing，ChIP-seq）鉴定了其DNA结合序列，并证实PA3898可直接与4个基因/操纵子的启动子区域结合，其中两个靶标为mexAB-oprM与phz2。本研究采用携带有TY1标签的PA3898的PAO1菌株，通过ChIP-seq鉴定与该调控因子互作的DNA序列。