ABSTRACT:
Pathogenic bacteria attack their host by secreting virulence factors that, in various ways, interrupt host defenses and damage their cells. Specific functions of many putative virulence factors, even from well-studied pathogens, are still unknown. Francisella tularensisis a class A pathogen and the causative agent of tularemia, a rare but potentially lethal disease that can be treated only with specialized antibiotics. Here we report the three-dimensional structure and preliminary analyses of the potential virulence factor, identified by the transcriptomic analysis of the F. tularensis disease models, that is encoded by the FTT_1539 gene. The structure of the FTT_1539 protein contains two sets of three-stranded antiparallel beta sheets, with a helix placed between the first and the second beta strand in each sheet. This structural motif, previously seen in virulence factors from other pathogens, was named the SHS2 motif and was identified to play a role in protein-protein interactions and small molecule recognition. Sequence and structure analysis identifies FTT_1539 as a founding member of a novel family of secreted proteins from a broad range of pathogenic bacteria, including Helicobacter pylori andMycobacterium tuberculosis. While the specific function of the proteins from this class is still unknown, their structural similarity to the H. pylori Tip-α protein that induces TNF-α and other chemokines through NF-κB activation suggests the existence of a common pathogen-host interference mechanism shared by multiple human pathogens.