Transcriptomic Profiling of Yersinia pseudotuberculosis Reveals Reprogramming of the Crp Regulon by Temperature and Uncovers Crp as a Master Regulator of Small RNAs

Aaron M. Nuss, Ann Kathrin Heroven, Barbara Waldmann, Jan Reinkensmeier, Michael Jarek, Michael Beckstette, Petra Dersch, Cynthia M. Sharma
2015 PLoS Genetics  
One hallmark of pathogenic yersiniae is their ability to rapidly adjust their life-style and pathogenesis upon host entry. In order to capture the range, magnitude and complexity of the underlying gene control mechanisms we used comparative RNA-seq-based transcriptomic profiling of the enteric pathogen Y. pseudotuberculosis under environmental and infectionrelevant conditions. We identified 1151 individual transcription start sites, multiple riboswitch-like RNA elements, and a global set of
more » ... sense RNAs and previously unrecognized trans-acting RNAs. Taking advantage of these data, we revealed a temperature-induced and growth phase-dependent reprogramming of a large set of catabolic/energy production genes and uncovered the existence of a thermo-regulated 'acetate switch', which appear to prime the bacteria for growth in the digestive tract. To elucidate the regulatory architecture linking nutritional status to virulence we also refined the CRP regulon. We identified a massive remodelling of the CRP-controlled network in response to temperature and discovered CRP as a transcriptional master regulator of numerous conserved and newly identified noncoding RNAs which participate in this process. This finding highlights a novel level of complexity of the regulatory network in which the concerted action of transcriptional regulators and multiple non-coding RNAs under control of CRP adjusts the control of Yersinia fitness and virulence to the requirements of their environmental and virulent life-styles. regulatory networks which adjust synthesis of the large repertoire of crucial virulence factors and fitness determinants. To uncover underlying control circuits, we determined the first in-depth single-nucleotide resolution transcriptome of Yersinia. This revealed important novel genetic information, such as global locations of transcriptional start sites, noncoding RNAs, potential riboswitches and provided a set of virulence-relevant expression profiles, which constitute a valuable tool for the research community. The analysis further uncovered a temperature-induced global reprogramming of central metabolic functions, likely to support intestinal colonization of the pathogen. This is accompanied by a major reorganization of the CRP regulon, which involves a multitude of regulatory RNAs. The primary consequence is a fine-tuned, coordinated control of metabolism and virulence through a plethora of environmentally controlled regulatory RNAs allowing rapid adaptation and high flexibility during life-style changes. Transcriptional Landscape of Y. pseudotuberculosis PLOS Genetics |
doi:10.1371/journal.pgen.1005087 pmid:25816203 pmcid:PMC4376681 fatcat:zdhpyjf5v5eqto4dertvhemdla