1. Functional Characterization of a Novel Hybrid Peptide with High Potency against Gram-negative Bacteria
- Author
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Ahmad Abualhaijaa, Karem H. Alzoubi, Yara Al Tall, Ammar Almaaytah, Majed M Masadeh, and Baha'a Al-Rawashdeh
- Subjects
Erythrocytes ,Gram-negative bacteria ,medicine.drug_class ,medicine.medical_treatment ,Antibiotics ,Antimicrobial peptides ,Microbial Sensitivity Tests ,Cathelicidin ,Microbiology ,03 medical and health sciences ,Drug Resistance, Multiple, Bacterial ,Ampicillin ,Gram-Negative Bacteria ,Drug Discovery ,Escherichia coli ,medicine ,Humans ,Potency ,030304 developmental biology ,Pharmacology ,0303 health sciences ,biology ,030306 microbiology ,Chemistry ,Drug Synergism ,Antimicrobial ,biology.organism_classification ,Recombinant Proteins ,Anti-Bacterial Agents ,Pseudomonas aeruginosa ,Peptides ,Bacteria ,medicine.drug - Abstract
Background: Multi-drug resistant infections are a growing worldwide health concern. There is an urgent need to produce alternative antimicrobial agents. Objective : The study aimed to design a new hybrid antimicrobial peptide, and to evaluate its antimicrobial activity alone and in combination with traditional antibiotics. Methods: 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. Results: 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. Conclusion: BMR-1 hybrid peptide is a promising candidate to treat resistant infectious diseases caused by gramnegative bacteria.
- Published
- 2020