An atlas of the binding specificities of transcription factors in Pseudomonas aeruginosa directs prediction of novel regulators in virulence
Tingting Wang,
Wenju Sun,
Ligang Fan,
Canfeng Hua,
Nan Wu,
Shaorong Fan,
Jilin Zhang,
Xin Deng,
Jian Yan
Affiliations
Tingting Wang
Department of Biomedical Sciences, City University of Hong Kong, Kowloon Tong, Hong Kong SAR, China
Wenju Sun
School of Medicine, Northwest University, Xi’an, China
Ligang Fan
Department of Biomedical Sciences, City University of Hong Kong, Kowloon Tong, Hong Kong SAR, China; School of Medicine, Northwest University, Xi’an, China
Canfeng Hua
Department of Biomedical Sciences, City University of Hong Kong, Kowloon Tong, Hong Kong SAR, China
Nan Wu
School of Medicine, Northwest University, Xi’an, China
Shaorong Fan
School of Medicine, Northwest University, Xi’an, China
Jilin Zhang
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Solna, Sweden
Xin Deng
Department of Biomedical Sciences, City University of Hong Kong, Kowloon Tong, Hong Kong SAR, China
Department of Biomedical Sciences, City University of Hong Kong, Kowloon Tong, Hong Kong SAR, China; School of Medicine, Northwest University, Xi’an, China
A high-throughput systematic evolution of ligands by exponential enrichment assay was applied to 371 putative TFs in Pseudomonas aeruginosa, which resulted in the robust enrichment of 199 unique sequence motifs describing the binding specificities of 182 TFs. By scanning the genome, we predicted in total 33,709 significant interactions between TFs and their target loci, which were more than 11-fold enriched in the intergenic regions but depleted in the gene body regions. To further explore and delineate the physiological and pathogenic roles of TFs in P. aeruginosa, we constructed regulatory networks for nine major virulence-associated pathways and found that 51 TFs were potentially significantly associated with these virulence pathways, 32 of which had not been characterized before, and some were even involved in multiple pathways. These results will significantly facilitate future studies on transcriptional regulation in P. aeruginosa and other relevant pathogens, and accelerate to discover effective treatment and prevention strategies for the associated infectious diseases.
