Genome-Wide Analysis of Gene Expression Noise Brought About by Transcriptional Regulation in Pseudomonas aeruginosa

The part of expression noise that is brought about by transcriptional regulation (represented here as NTR) is an important criterion for estimating the regulatory mode of a gene. However, characterization of NTR is an under-explored area, and there is little knowledge regarding the genome-wide NTR in the model pathogen Pseudomonas aeruginosa. Here, with a library of dual-color transcriptional reporters, we estimated the NTR for over 90% of the promoters in P. aeruginosa. Most promoters exhibit low NTR, while 42 and 115 promoters with high NTR were screened out in the exponential and the stationary growth phases, respectively. Specifically, a rearrangement of NTR was found in promoters involved in amino acid metabolism when bacteria enter the exponential phase. In addition, during the stationary phase, high NTR was found in a wide range of iron-related promoters involving siderophore synthesis and heme uptake, ExsA-regulated promoters involving bacterial virulence, and FleQ-regulated promoters involving biofilm development. We also found a large-scale negative dependence of transcriptional regulation between high-NTR promoters belonging to different functional categories. Our findings offer a global view of transcriptional heterogeneity in P. aeruginosa. IMPORTANCE The phenotypic diversity of Pseudomonas aeruginosa is frequently observed in research, suggesting that bacteria adopt strategies such as bet-hedging to survive ever-changing environments. Gene expression noise (GEN) is the major source of phenotypic diversity. Large GEN from transcriptional regulation (represented as NTR) represent an evolutionary necessity to maintain the copy number diversity of certain proteins in the population. Here, we provide a system-wide view of NTR in P. aeruginosa under nutrient-rich and stressed conditions. High NTR was found in genes involved in flagella biosynthesis and amino acid metabolism under both conditions. Specially, iron acquisition genes exhibited high NTR in the stressed condition, suggesting a great diversity of iron physiology in P. aeruginosa. We further revealed a global negative dependence of transcriptional regulation between those high-NTR genes under the stressed condition, suggesting a mutually exclusive relationship between different bacterial survival strategies.