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The multifunctional role of the pallilysin‐associated T reponema pallidum protein, Tp 0750, in promoting fibrinolysis and extracellular matrix component degradation
Author(s) -
Houston Simon,
Russell Shan,
Hof Rebecca,
Roberts Alanna K.,
Cullen Paul,
Irvine Kyle,
Smith Derek S.,
Borchers Christoph H.,
Tonkin Michelle L.,
Boulanger Martin J.,
Cameron Caroline E.
Publication year - 2014
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.12482
Subject(s) - biology , proteolysis , serine protease , plasmin , extracellular matrix , fibronectin , matrix metalloproteinase , microbiology and biotechnology , metalloproteinase , proteases , protease , biochemistry , enzyme
Summary The mechanisms that facilitate dissemination of the highly invasive spirochaete, T reponema pallidum , are incompletely understood. Previous studies showed the treponemal metalloprotease pallilysin ( Tp 0751) possesses fibrin clot degradation capability, suggesting a role in treponemal dissemination. In the current study we report characterization of the functionally linked protein Tp 0750. Structural modelling predicts Tp 0750 contains a von W illebrand factor type A ( vWFA ) domain, a protein‐protein interaction domain commonly observed in extracellular matrix ( ECM )‐binding proteins. We report Tp 0750 is a serine protease that degrades the major clot components fibrinogen and fibronectin. We also demonstrate Tp 0750 cleaves a matrix metalloprotease ( MMP ) peptide substrate that is targeted by several MMPs , enzymes central to ECM remodelling. Through proteomic analyses we show Tp 0750 binds the endothelial fibrinolytic receptor, annexin A 2, in a specific and dose‐dependent manner. These results suggest Tp 0750 constitutes a multifunctional protein that is able to (1) degrade infection‐limiting clots by both inhibiting clot formation through degradation of host coagulation cascade proteins and promoting clot dissolution by complexing with host proteins involved in the fibrinolytic cascade and (2) facilitate ECM degradation via MMP ‐like proteolysis of host components. We propose that through these activities Tp 0750 functions in concert with pallilysin to enable T . pallidum dissemination.