The Inhibition And Application Of A Novel Antibacterial Peptide Against Oral Pathogens And Biofilm

Dental caries and periodontal disease are highly prevalent in humans. They are caused primarily by changes in homeostasis of the oral cavity, which result in overgrowth of Streptococcus mutans and other pathogenic bacteria. In addition, these opportunistic pathogens, such as S. mutans, Streptococcus sobrinus, Porphyromonas gingivalis can produce extracellular polysaccharides and other substances to form a thin film on the surface of the tooth at their metabolic process. After then, the other bacteria begin to adsorb on the biofilm. The biofilm will develop into plaque when the thickness reaches a certain level. And the plaque is called "initiating factor" of oral disease. So if we want to prevent or treatment of the oral diseases, we should not only kill the bacteria in the mouth, but also inhibit the formation and development of plaque biofilm.We investigated the activity of a novel antimicrobial peptide (AMP) ZXR-2 derived from scorpion venom against oral bacteria. ZXR-2 showed broad-spectrum activity against a variety of Gram-positive and Gram-negative bacteria, and the MIC of Escherichia coli was 4 ?M about 90 times lower than penicillin. Time-course killing assays indicated that ZXR-2 killed bacteria rapidly, and killed most bacterial cells within 5 min at 4×MIC. The mechanism of action of ZXR-2 involved disruption of the cell membrane, as observed by SEM. In comparison, ZXR-2 had little effect on mammalian cells, at 8-16?M concentration on three hours, about 15% of the red blood cell hemolysis. Moreover, ZXR-2 inhibited the formation of S. mutans biofilm, but had a limited effect on mature biofilms. Based on its potent antimicrobial activity, rapid killing, and inhibition of the formation of S. mutans biofilm, ZXR-2 represents a potential therapeutic for the prevention and treatment of dental caries.