The Addition of a Synthetic LPS-Targeting Domain Improves Serum Stability While Maintaining Antimicrobial, Antibiofilm, and Cell Stimulating Properties of an Antimicrobial Peptide

Multi-drug resistant (MDR) bacteria and their biofilms are a concern in veterinary and human medicine. Protegrin-1 (PG-1), a potent antimicrobial peptide (AMP) with antimicrobial and immunomodulatory properties, is considered a potential alternative for conventional antibiotics. AMPs are less stable and lose activity in the presence of physiological fluids, such as serum. To improve stability of PG-1, a hybrid peptide, SynPG-1, was designed. The antimicrobial and antibiofilm properties of PG-1 and the PG-1 hybrid against MDR pathogens was analyzed, and activity after incubation with physiological fluids was compared. The effects of these peptides on the IPEC-J2 cell line was also investigated. While PG-1 maintained some activity in 25% serum for 2 h, SynPG-1 was able to retain activity in the same condition for up to 24 h, representing a 12-fold increase in stability. Both peptides had some antibiofilm activity against Escherichia coli and Salmonella typhimurium. While both peptides prevented biofilm formation of methicillin-resistant Staphylococcus aureus (MRSA), neither could destroy MRSA’s pre-formed biofilms. Both peptides maintained activity after incubation with trypsin and porcine gastric fluid, but not intestinal fluid, and stimulated IPEC-J2 cell migration. These findings suggest that SynPG-1 has much better serum stability while maintaining the same antimicrobial potency as PG-1.