Functional peptides implicated in the virulence of the enteric pathogen Yersinia pseudotuberculosis
The enteric pathogen Yersinia pseudotuberculosis has evolved a plethora of different pathogenicity factors, which promote survival and proliferation in its mammalian hosts. Until today, many common and species-specific strategies have been discovered that allow a coordinated and spatiotemporal expression of its virulence determinants. Our recent tissue dual RNA-Seq analysis of Y. pseudotuberculosis residing within the lymphatic tissue of mice revealed the entire repertoire of genes, which are transcribed during infection. A bioinformatics approach uncovered that many of the detected transcripts, including several non-coding RNAs and multiple virulence gene-associated transcripts, contain short open reading frames (sORFs) for small peptides (20-50 aa), so-called µ-proteins. First experiments confirmed translation of about 30% of the tested subset. The genomic context and regulation of some predicted µ-proteins indicate that they display potent functions that contribute to virulence. In the present project we aim to decipher the µ-protein repertoire of the enteric pathogen Y. pseudotuberculosis using ribosome profiling and proteomics to validate our bioinformatics approach. A small selection of the identified µ-protein candidates, that are most likely to play a crucial role in virulence, will be further characterized. To do so, we want to tackle their regulation, molecular function, cellular localization, interaction partners and role in pathogenesis. A major focus will be the characterization of µ-proteins, which are co-regulated with the Yersinia type III secretion system (T3SS). The T3SS injects anti-phagocytic Yop effector proteins into innate immune cells of the host to prevent phagosomal killing.
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Professor Dr. Ruth Anne Schmitz-Streit
DFG - German Research Foundation