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Global transcription factors analyses reveal hierarchy and synergism of regulatory networks and master virulence regulators in Pseudomonas aeruginosa 2

ABSTRACT: 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.

ORGANISM(S): Pseudomonas aeruginosa PAO1

PROVIDER: GSE271817 | GEO | 2025/03/31

REPOSITORIES: GEO

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Global transcription factors analyses reveal hierarchy and synergism of regulatory networks and master virulence regulators in Pseudomonas aeruginosa

Project description: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.

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2013-02-21 | E-GEOD-43641 | biostudies-arrayexpress

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Project description:Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen of humans, most notably those with cystic fibrosis or whose immune systems are compromised. As a global regulator, RpoN has been characterized to control a group of virulence-related factors and quorum sensing (QS) genes in P. aeruginosa, but its detailed molecular regulatory mechanism is largely elusive. To further gain insights into the direct targets of RpoN in vivo, this study focused on identifying the potential targets of RpoN directly regulating QS system and T6SS. We performed a chromatin immunoprecipitation coupled to high-throughput sequencing (ChIP-seq) assay that identified 1, 068 binding sites of RpoN, including mostly metabolic genes, a group of genes in QS (lasI, rhlI and pqsR) and type VI secretion system (T6SS) (hcpA and hcpB). The direct regulation of these genes by RpoN has been biochemically and genetically verified. Results revealed that, on one hand, the deletion of rpoN resulted in reduced production of pyocyanin, motility and proteolytic activity. On the other hand, the production of rhamnolipids and biofilm formation was higher in the RpoN mutant than in the wild-type. In sum, the results indicated that RpoN had direct and profound effects on QS and T6SS, which provides new cues to better understand the detailed regulatory networks of virulence.

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