Broad-spectrum antimicrobial peptides (AMPs) kill bacteria indiscriminately, increasing the possibility of an ecological imbalance in the microbiota. To solve this problem, new types of AMPs, which kill pathogenic bacteria without breaking the micro-ecological balance of the body, were proposed. Here, we successfully designed a targeting AMP, S2, which is a fusion peptide composed of a species-specific targeting domain and broad-spectrum AMP domain. In the current study, S2 showed specific killing activity against Staphylococcus aureus, and almost no resistance induced compared to penicillin. Mechanism studies indicated that S2 killed S. aureus by destroying the bacterial membrane. Meanwhile, S2 possessed excellent salt-tolerance properties and biocompatibility. Importantly, S2 exhibited perfect treatment efficacy against an S. aureus subcutaneous infection model and remained nontoxic. In conclusion, this study provides a promising strategy for designing specific AMPs against growing bacterial infections.

Candida albicans, an opportunistic fungus, causes dental caries and contributes to mucosal bacterial dysbiosis leading to a second infection. Furthermore, C.albicans forms biofilms that are resistant to medicinal treatment. To make matters worse, antifungal resistance has spread (albeit slowly) in this species. Thus, it has been imperative to develop novel, antifungal drug compounds. Herein, a peptide was engineered with the sequence of RRFSFWFSFRR-NH2; this was named P19. This novel peptide has been observed to exert disruptive effects on fungal cell membrane physiology. Our results showed that P19 displayed high binding affinity to lipopolysaccharides (LPS), lipoteichoic acids (LTA) and the plasma membrane phosphatidylinositol (PI), phosphatidylserine (PS), cardiolipin, and phosphatidylglycerol (PG), further indicating that the molecular mechanism of P19 was not associated with the receptor recognition, but rather related to competitive interaction with the plasma membrane. In addition, compared with fluconazole and amphotericin B, P19 has been shown to have a lower potential for resistance selection than established antifungal agents.