Polyphenol Oxidases as Antiadhesins

Doyle, Ronald

Abstract

Several years of research have shown that many oral diseases require bacteria. The bacteria may produce toxins or may elicit host inflammatory responses. In order for bacteria to produce oral diseases, particularly dental caries and periodontal diseases, there is a requirement that the pathogens adhere to and subsequently colonize host tissues. This research is directed to the discovery of a new class of microbial anti- adhesins. It has been observed that plant polyphenol oxidases (PPOs) can effectively abolish adhesion of oral streptococci and other pathogens to various substrata. The research will concentrate on, but not be restricted to, microbial lectin targets on oral pathogens. The proposed research will focus on S. mutans and S. sobrinus, bacteria known to be involved in human dental caries, as well as selected periodontopathogens. By use of a protease-free mushroom PPO, this research will: 1. Define how the PPO inhibits the glucan-binding lectins and glucosyltransferases of the streptococci. 2. Determine the conditions in which PPO will prevent coaggregation reactions between selected coaggregating pairs, including streptococci, actinomyces and gram-negative periodontopathogens. 3. Show that PPO reduces the ability of several oral pathogens to hemagglutinate. 4. Determine if protease activities of Porphyromonas gingivalis are reduced simultaneously with loss of adhesin function upon incubation of the cells with PPO. 5. Define the conditions describing the ability of PPO to reduce bacterial adhesion to collagen and fibronectin, extracellular matrix receptors for many oral bacteria. 6. Study how PPO abolishes the ability of Streptococcus pyogenes to bind a human laryngeal cell line and to bind to soluble fibronectin. A goal of this research is to define how PPO(s) can inactivate adhesins of oral pathogens. A long term goal is to determine if PPO can be utilized in preventing or treating oral microbial diseases.