Global transcription factors analyses reveal hierarchy and synergism of regulatory networks and master virulence regulators in Pseudomonas aeruginosa
The transcription factor regulatory network (TRN) in Pseudomonas aeruginosa is complicated and involves multiple regulators responding to various environmental signals and physiological cues by regulating gene expression. P. aeruginosa utilizes versatile virulent determinants to exert its virulence, including biofilm formation, quorum sensing (QS), Type III (T3SS) and Type IV (T6SS) secretion system, motility, siderophore production, oxidative stress resistance, and antibiotic resistance, which under the control of TRN. Herein, ChIP-seq was applied to investigate the binding sites of 158 TFs in P. aeruginosa PAO1 strain. The results revealed a total of 30,481 significant binding peaks in the genome, more than half of which were located in the promoter regions. To furthermore decode diverse regulatory relationships among TFs, the hierarchical network was assembled into three levels: top, middle, and bottom. Thirteen ternary regulatory motifs revealed flexible relations of TFs in small hubs, and a comprehensive co-association atlas was established and enriched three high-associated clusters. A total of 32 TFs were identified as master regulators in regulating virulence-related pathways, and 34 TFs were involved in four metabolism pathways significantly. These results will provide significant insight into understanding the pathogenesis mechanisms of P. aeruginosa and relevant bacteria and contributing to developing effective therapies for diseases caused by infection. Overall design: ChIP-seq analyses of genomic regulators in Pseudomonas aeruginosa