Functional Characterization of a Novel Hybrid Peptide with High Potency against Gram-negative Bacteria

Abstract

Multi-drug resistant infections are a growing worldwide health concern. There is an urgent need to produce alternative antimicrobial agents. The study aimed to design a new hybrid antimicrobial peptide, and to evaluate its antimicrobial activity alone and in combination with traditional antibiotics. Herein, we designed a novel hybrid peptide (BMR-1) using the primary sequences of the parent peptides Frog Esculentin-1a and Monkey Rhesus cathelicidin (RL-37). The positive net charge was increased, and other physicochemical parameters were optimized. The antimicrobial activities of BMR-1 were tested against control and multi-drug resistant gram-negative bacteria. BMR-1 adopted a bactericidal behavior with MIC values of 25-30 µM. These values reduced by over 75% upon combination with conventional antibiotics (levofloxacin, chloramphenicol, ampicillin, and rifampicin). The combination showed strong synergistic activities in most cases and particularly against multi-drug resistance P. aeruginosa and E. coli. BMR-1 showed similar potency against all tested strains regardless of their resistant mechanisms. BMR-1 exhibited no hemolytic effect on human red blood cells with the effective MIC values against the tested strains. BMR-1 hybrid peptide is a promising candidate to treat resistant infectious diseases caused by gramnegative bacteria.