Purification and characterization of a novel cysteine proteinase (periodontain) from Porphyromonas gingivalis - Evidence for a role in the inactivation of human alpha(1)-proteinase inhibitor

Periodontal disease is characterized by inflammation of the periodontium ma nifested by recruitment of neutrophils, which can degranulate, releasing po werful proteinases responsible for destruction of connective tissues, and e ventual loss of tooth attachment. Although the presence of host proteinase inhibitors (serpins) should minimize tissue damage by endogenous proteinase s, this is not seen clinically, and it has been speculated that proteolytic inactivation of serpins may contribute to progression of the disease. A ma jor pathogen associated with periodontal disease is the Gram-negative anaer obe Porphyromonas gingivalis, and in this report, we describe a novel prote inase that has been isolated from culture supernatants of this organism tha t is capable of inactivating the human serpin, alpha(1)-proteinase inhibito r, the primary endogenous regulator of human neutrophil elastase, This new enzyme, referred to as periodontain, belongs to the cysteine proteinase fam ily based on inhibition studies and exists as a 75-kDa heterodimer, Further more, periodontain shares significant homology to streptopain, a proteinase from Streptococcus pyogenes, and prtT, a putative proteinase from P, gingi valis. Clearly, the presence of this enzyme, which rapidly inactivates alph a(1)-proteinase inhibitor, could result in elevated levels of human neutrop hil elastase clinically detected in periodontal disease and should be consi dered as a potential virulence factor for P, gingivalis.