Functional peptides implicated in the virulence of the enteric pathogen Yersinia pseudotuberculosis
Helmholtz Centre for Infection research Braunschweig (Germany), Molecular Infection Biology
The enteric pathogen Yersinia pseudotuberculosis evolved a plethora of different pathogenicity factors which promote survival and and proliferation in their mammalian hosts. Moreover, many common and species-specific strategies have been discovered how these bacteria adjust and coordinate spatiotemporal expression of virulence determinants and complex virulence control networks exist which involve a large repertoire of transcriptional and post-transcriptional regulators. Our recent Tissue dual RNA-Seq analysis of Y. pseudotuberculosis residing in lymphatic tissue revealed the entire repertoire of genes which are transcribed during infection conditions. A bioinformatics approach revealed that many of the detected transcripts, including several non-coding RNAs and multiple virulence gene transcripte, contain short reading frames (sORFs) for small peptides (20-60 aa), so-called small proteins. First experiments confirmed translation of about 30% of the tested subset, and the gene context and regulation of some predicted small proteins indicate that they display potent functions that contribute to virulence. In the present project we aim to decipher the small protein repertoire of the enteric pathogen Y. pseudotuberculosis using ribosome profiling and proteomics to validate our bioinformatics approach. From the set of identified small proteins a small selection of the candidates, that are most likely to play a crucial role in virulence, will be further characterized to tackle their regulation, molecular function and role in pathogenesis. A major focus will be the characterization of small proteins, which are coregulated with the Yersinia type III secretion system which injects antiphagocytic Yop effector proteins into innate immune cells of the host to prevent phagosomal killing.
- Nuss AM., Beckstette M., Pimenova M., Schmühl C., Opitz W., Pisano F., Heroven AK., and Dersch P. Tissue dual RNA-seq allows fast discovery of infection-specific functions and riboregulators shaping host-pathogen transcriptome. (2017), Proc. Natl. Acad. Sci. USA 114(5):E791-E800.
- Nuss AM., Schuster F., Roselius L., Klein J., Bücker R., Herbst K., Heroven AK., Pisano F., Wittmann C., Münch R., Müller J., Jahn D., and Dersch P. A precise temperature-responsive bistable switch controlling virulence (2016). PLoS Pathogens 12(12):e1006091.
- Wang H., Avican K., Ertmann S., Nuss A.M., Dersch P., Fällman M., Edgren T, Wolf-Watz, H. Increased plasmid copy number is essential for Yersinia T3SS function and virulence (2016).Science 353(6298): 492-495.
- Righetti R., Nuss AM., Twittenhoff C., Beele S., Urban K., Stadler P., Dersch P., and Narberhaus F. The temperature-responsive RNA structurome of Yersinia pseudotuberculosis (2016), Proc. Natl. Acad. Sci. USA 113(26):7237-42.
- Nuss A.M., Heroven AK., Waldmann B., Reinkensmeyer J., Jarek M., Beckstette M. & Dersch P. (2015) Transcription profiling by RNAseq reveals Crp as master regulator of small regulatory RNAs in Yersinia pseudotuberculosis , PLoS Genetics, 11(3):e1005087.