LAUSR

The outer membrane proteins (OMPs) of Treponema pallidum subsp. Pallidum (T. pallidum), the etiological agent of the sexually transmitted disease syphilis, has long been a hot research topic. Despite many hurdles to studying the pathogen, especially the inability to manipulate T. pallidum in vitro genetically1, considerable progress has been made in elucidating the structure, pathogenesis, and functions of T. pallidum OMPs. In this review, we integrate this information to garner fresh insights into the role of OMPs in the diagnosis, pathogenicity, and vaccine development of T. pallidum. Collectively, the essential scientific discussions herein should provide a framework for understanding the current status and prospects of T. pallidum OMPs. Decades ago, researchers postulated that the poor surface antigenicity of T. pallidum is the basis for its ability to cause persistent infection. Still, they believed that the mysterious properties of T. pallidum should not be attributed to the presence of the outer membrane proteins (OMPs). Subsequent studies revealed that the OM, which lacks integral membrane proteins, prevents antibody binding2. Since the advent of recombinant DNA technology, the fragility of the OM, low protein content, and the lack of sequence relatedness between T. pallidum and Gram-negative OMPs have complicated efforts to characterize molecules residing at the host-pathogen interface. These hurdles have been overcome by using the genomic sequence with computational tools to identify proteins predicted to form beta barrels, the hallmark conformation of OMPs in many organisms. Diverse methodologies have also confirmed that some candidate OMPs from amphiphilic β-barrels are surface-exposed in T. pallidum. These studies have led to a structural homology model for BamA and established the bipartite topology of the T. pallidum repeat (Tpr) family of proteins. Recent bioinformatics has identified several structural orthologs for well-characterized Gram-negative OMPs, suggesting that the T. pallidum OMPs are more Gram-negative-like than previously supposed. Lipoprotein adhesins and proteases on the spirochete surface also may contribute to disease pathogenesis and protective immunity.