Researchers discovered a new peptide called RK22 from a leech that can kill regular and drug‑resistant Staph bacteria at low doses. It stops the bacteria from forming protective biofilms, works well in blood, doesn’t harm human cells or cause blood clots, and protected animals from infection in tests. While it isn’t available for personal use yet, it shows promise as a future anti‑infection drug.

<i>Staphylococcus aureus</i> (<i>S. aureus</i>) infections are a leading cause of morbidity and mortality, which are compounded by drug resistance. By manipulating the coagulation system, <i>S. aureus</i> gains a significant advantage over host defense mechanisms, with hypercoagulation induced by <i>S. aureus</i> potentially aggravating infectious diseases. Recently, we and other researchers identified that a higher level of LL-37, one endogenous antimicrobial peptide with a significant killing effect on <i>S. aureus</i> infection, resulted in thrombosis formation through the induction of platelet activation and potentiation of the coagulation factor enzymatic activity. In the current study, we identified a novel antimicrobial peptide (RK22) from the salivary gland transcriptome of <i>Hirudinaria manillensis</i> (<i>H. manillensis</i>) through bioinformatic analysis, and then synthesized it, which exhibited good antimicrobial activity against <i>S. aureus</i>, including a clinically resistant strain with a minimal inhibitory concentration (MIC) of 6.25 &#x3bc;g/mL. The RK22 peptide rapidly killed <i>S. aureus</i> by inhibiting biofilm formation and promoting biofilm eradication, with good plasma stability, negligible cytotoxicity, minimal hemolytic activity, and no significant promotion of the coagulation system. Notably, administration of RK22 significantly inhibited <i>S. aureus</i> infection and the clinically resistant strain in vivo. Thus, these findings highlight the potential of RK22 as an ideal treatment candidate against <i>S. aureus</i> infection.