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ARS Home » Midwest Area » Ames, Iowa » National Animal Disease Center » Infectious Bacterial Diseases Research » Research » Publications at this Location » Publication #314736

Title: The host-interacting proteins Tp0750 and Pallilysin; conservation among treponemes and restriction of proteolytic capacity to Treponema pallidum

item HOUSTON, SIMON - University Of Victoria
item TAYLOR, JOHN - University Of Victoria
item DENCHEV, YAVOR - University Of Victoria
item HOF, REBECCA - University Of Victoria
item Zuerner, Richard
item CAMERON, CAROLINE - University Of Victoria

Submitted to: American Society for Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/6/2015
Publication Date: N/A
Citation: N/A

Interpretive Summary: Bacteria in the genus Treponema cause, or are associated with a variety of human and animal diseases, including bovine digital dermatitis, a debilitating infection of the hoof, and a leading cause of lameness in dairy and beef cattle. Treponema are difficult to isolate from infected tissue, grow poorly, and are difficult to characterize. Consequently, few traits have been identified that clearly contribute to disease processes from this group of bacteria. Previous studies showed that two proteins from T. pallidum, encoded by the genes Tp0750 and Tp0751, bind to and degrade host proteins. Genes related to Tp0750 and Tp0751 are found in several other pathogenic Treponema species, including T. phagedenis and T. denticola, a species associated with human periodontitis, but it is unknown whether or not they can degrade host proteins. In this study recombinant DNA technology was used to clone Tp0750 and Tp0751 genes from Treponema species, the proteins expressed, purified, and tested for the ability to degrade host proteins. Significant degradation of selected host proteins was only detected when the T. pallidum proteins were tested. As this is the most invasive Treponema species known, it is thought that Tp0750/Tp0751 may have an important role in bacterial invasion and dissemination. In contrast, T. phagedenis and T. denticola tend to remain localized near the initial lesion and do not disseminate to distal parts of the host body, and this limitation may be due, in part, to the inability of their Tp0750/Tp0751 proteins to degrade host proteins.

Technical Abstract: The spirochete Treponema pallidum is the causative agent of syphilis, a chronic, sexually transmitted bacterial infection characterized by multiple symptomatic and asymptomatic stages. Treponema pallidum is significantly more invasive than other treponemal species, being able to cross both the blood-brain and placental barriers and rapidly disseminating via the bloodstream to tissue sites distant from the site of initial infection. Previously, the co-associated T. pallidum proteins, Tp0750 and pallilysin (Tp0751), were shown to degrade host proteins central to blood coagulation and basement membrane integrity, suggesting a role for these proteins in T. pallidum dissemination and tissue invasion. In the current study, we assessed the level of sequence conservation of pallilysin and Tp0750 orthologs among treponemal species and determined the proteolytic potential of pallilysin/Tp0750 orthologs from Treponema denticola and Treponema phagedenis-like digitial dermatitis treponemes. These analyses showed that, except for the rabbit venereal syphilis-causing Treponema paraluiscuniculi, there was a lack of significant sequence conservation with pallilysin orthologs from other treponemes, including within the active site residues that have been defined for pallilysin. Conversely, significant conservation was observed among Tp0750 orthologs from pathogenic treponemes. Further, in vitro host component degradation assays demonstrated that pallilysin and Tp0750 orthologs from only T. pallidum, and not the less invasive treponemes tested, were capable of degrading host proteins. The results of this study show that, although pallilysin/Tp0750 orthologs are found in other treponemes, the degradative capabilities of the orthologs are confined to T. pallidum and thus positively correlate with treponemal invasive capacity.