Functions of small proteins in bacterial physiology and virulence

High-throughput sequencing has generated millions of genome sequences, from which potential functions are inferred by gene prediction.

To avoid excessive annotation of hypothetical but non-functional genes, predictions systematically exclude short open reading frames.

Yet, accumulating evidence suggests that many unannotated small proteins (s-proteins) are expressed and carry out important functions. At present, the function of this “dark proteome” of s-proteins is largely unknown.

The proposed project focuses on in-depth functional characterization of s-proteins in the bacterial pathogen Salmonella, and is divided into four parts.

Characterizing the regulation and physiological impact of small endogenous toxins will provide clues as to why such “dangerous” genes are conserved.

Assessing the regulatory function of a horizontally transferred s-protein and its impact during anaerobic growth will give insights into bacterial survival in the infected host.

Identification of small RNA-binding proteins will establish a frame-work for infection-relevant post-transcriptional regulation.

Finally, we will characterize the functions of s-proteins that act as virulence factors by localizing to the bacterial membrane, or through secretion into eukaryotic host cells.

The obtained results will pioneer our understanding of how s-proteins shape bacterial physiology and pathogenicity, which may provide new avenues for developing effective treatments of infectious disease.