A short novel antimicrobial peptide BP100-W with antimicrobial, antibiofilm and anti-inflammatory activities designed by replacement with tryptophan

BP100 is a short cationic antimicrobial peptide (AMP) designed using a combinatorial chemistry approach based on the cecropin A-melittin hybrid. It displays potent antimicrobial activity against gram-negative bacteria and low toxicity toward eukaryotic cells. To develop a short AMP with potent cell selectivity, antibiofilm and anti-inflammatory activities, we designed a newly BP100 analog, BP100-W, in which Leu-3 at the hydrophobic face of BP100 was replaced by Trp. BP100-W possessed better cell selectivity, with a 1.7-fold higher therapeutic index than BP100. BP100-W displayed more effective synergistic activity when combined with several antibiotics, such as chloramphenicol, ciprofloxacin and oxacillin, compared to BP-100. BP100-W also exhibited stronger antibiofilm activity than BP100 in inhibiting biofilm formation by multidrug-resistant Pseudomonas aeruginosa (MDRPA) and eradicating the preformed biofilms of MDRPA. Moreover, unlike BP100, BP100-W significantly suppressed the production and expression of lipopolysaccharide (LPS)-induced pro-inflammatory cytokines, such as the tumor necrosis factor-α and nitric oxide. Boron-dipyrromethene-TR-cadaverine displacement assay demonstrated that the inhibitory activity of BP100-W on LPS-induced inflammation in RAW 264.7 cells may be due to increased direct interaction with LPS. Our results suggest that BP100-W exhibits potential for future use as an antimicrobial, antibiofilm and anti-inflammatory agent.