Transcriptomic profiling of Yersinia pseudotuberculosis uncovers reprogramming of the Crp regulon and Crp as master regulator of sRNAs

Many bacterial pathogens, including pathogenic yersiniae, cycle between environmental sources and mammalian hosts. Adaptation of their repertoire of fitness and virulence factors to the different natural habitats and host niches is achieved through the concerted action of transcriptional and post-transcriptional gene control mechanisms. This study used comparative RNA-seq-based transcriptomic profiling to capture the range and complexity of control mechanisms of the enteric pathogen Y. pseudotuberculosis under environmental and infection-relevant conditions. We identified 1151 individual transcription start sites, multiple riboswitch-like RNA elements, and a global set of small non-coding RNAs (sRNAs), including numerous antisense 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 sRNAs which participate in this process. The primary consequence is a fine-tuned co-regulation of metabolism and virulence through a plethora of environmentally controlled sRNAs allowing rapid adaptation and high flexibility during life-style changes.