Antimicrobial Peptide CFH3 from Human Saliva: A Novel Inhibitor of <i>Staphylococcus hemolyticus</i> and Its Application in Chewing Gum

<i>Staphylococcus hemolyticus</i> is a primary pathogen in oral and maxillofacial space infections, against which antimicrobial peptides in human oral saliva may offer protection. In this study, an antimicrobial peptide, CFH3 (RPYFPVAVGK), derived from human complement factor H of saliva, was investigated through bioinformatics analysis. CFH3 exhibited a minimum bactericidal concentration (MBC) of 7.8 μg/mL against <i>S. hemolyticus</i>, eliminating bacteria at 1 × MBC by targeting intracellular DNA and proteins without cell membrane disruption. At 2 × MBC, CFH3 induced cell membrane disruption and leakage of cellular contents. CFH3 exhibited high biosafety, demonstrating low toxicity to human liver cells (LO2) with a 100% viability rate at 2 × MBC. Besides, its hemolysis rate remained below 5% even at 8 × MBC. A chewing gum containing 0.02% CFH3 was successfully formulated, releasing 62.53 ± 0.76% (312.64 ± 3.79 μg/mL) of the compound within 20 min of chewing. Furthermore, in artificial saliva, 125 μg/mL CFH3 significantly inhibited <i>S. hemolyticus</i>. Overall, these findings provide valuable insights into the functional role of peptides derived from oral saliva and their potential application in oral health and the food industry.