Small proteins implicated in the virulence of the enteric pathogen Yersinia pseudotuberculosis

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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 virulence strategies have been discovered but their coordinated and spatiotemporal expression and function is still not fully understood. Recent discoveries made evident that small proteins exist that might participate in these processes. Our recent ribosome profiling (Ribo-seq)/RNA-Seq of Y. pseudotuberculosis, grown under three different virulence-relevant conditions, revealed 14 expressed short open reading frames (sORFs) for small proteins (21-60 aa) encoded on the Yersinia virulence plasmid. This plasmid encodes a type III secretion system (T3SS) that injects effector proteins (Yops) into host innate immune cells to prevent the elimination of Yersinia by phagocytosis. The identified sORFs fall in three different categories: (i) small protein candidates implicated in the copy number of the Yersinia virulence plasmid, (ii) small proteins affecting the expression of the major transcriptional activator LcrF of the T3SS/Yop machinery, and (iii) small proteins affecting the secretion of the Yop effectors. A subset of the identified candidates, which are predicted to influence one of these different virulence-relevant functions, has been selected, validated and shown to influence the synthesis and/or secretion of the Yop proteins. Based on these results our main tasks in this project are to elucidate their regulation or regulatory mechanisms, their molecular function, interaction partners, cellular localization, and their role in pathogenesis.