Characterizing the role of YjiS in Salmonella virulence

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The first funding period was used to develop an integrative workflow combining new and existing datasets with the aim to compile a global overview of sORFs in the model human pathogen Salmonella enterica serovar Typhimurium, with special emphasis on sORFs with putative roles in bacterial virulence. The pipeline was designed to be universal applicable to other organisms and research question underlining its usefulness for a broader research community. The applicability of the proposed approach was demonstrated by novel insights into MgrB activity as well as the prioritization of the small DUF1127 domain protein YjiS as candidate for in-depth analysis in the second funding period. We now plan to use advanced techniques such as Dual RNA-seq and ribosome profiling, together with classical molecular biology approaches, to identify the regulon and interactome of YjiS and the impact of this small protein on Salmonella virulence. At the end of the project we will have performed an in-depth analysis of the role of YjiS in regulating virulence during macrophages infection. We will investigate this from different points of view, such as the pathways YjiS might be involved in, and the changes it induces in the host response to infection. We will describe the molecular mechanism of action that YjiS employs, and draw a comprehensive picture of how it affects different aspects of virulence. In parallel, we will initiate validation of our newly predicted STsORFs and perform a preliminary analysis to identify the ones with an infection phenotype. With this, we will have obtained a better picture of how small proteins are used by Salmonella to adapt to and manipulate the host environment.