There is great interest in the development of antimicrobial peptides as a potentially novel class of antimicrobial agents. Several structural determinants are responsible for the antimicrobial and cytolytic activity of antimicrobial peptides. In our study, a new synthetic peptide analog, AamAP1-Lysine from the naturally occurring scorpion venom antimicrobial peptide AamAP1, was designed by modifying the parent peptide in order to increase the positive charge and optimize other physico-chemical parameters involved in antimicrobial activity. AamAP1-Lysine displayed potent antibacterial activity against Gram-positive and Gram-negative bacteria. The minimum inhibitory concentration was in the range of 5 to 15 µM with a 10 fold increase in potency over the parent peptide. The hemolytic and antiproliferative activity of AamAP1-Lysine against eukaryotic mammalian cells was minimal at the concentration range needed to inhibit bacterial growth. The antibacterial mechanism analysis indicated that AamAP1-Lysine is probably inducing bacterial cell death through membrane damage and permeabilization determined by the release of β-galactosidase enzyme from peptide treated E. coli cells. DNA binding studies revealed that AamAP1-Lysine caused complete retardation of DNA migration and could display intracellular activities in addition to the membrane permeabilization mode of action reported earlier. In conclusion, AamAP1-Lysine could prove to be a potential candidate for antimicrobial drug development in future studies.

Background and purpose: The world is heading to a post-antibiotic era where the treatment of bacterial infections will not be possible even with well-known last-line antibiotics. Unfortunately, the emergence of multidrug resistant bacterial strains is uncontrollable, and the humanity will face a life-threatening fate unless new antimicrobial agents with new bacterial target sites are promptly developed. Herein, we design a hybrid antimicrobial peptide (B1) from helical parts taken from the parent peptides: LL-37 and BMAP-27. The purpose of this design is to improve the potency and enhance the toxicity profile of the parent peptides. Methods: Rational design was used to hybridize two antimicrobial peptides, in which two helical parts from the bovine analog BMAP-27, and the human cathelicidin LL-37 were used to generate a novel peptide (B1). The physicochemical properties were checked using in silico methods. The antimicrobial activities were tested against nine control and resistant strains of Gram-positive and Gram-negative bacteria. On the other hand, the antibiofilm activities were tested against four resistant strains. The cytotoxicity on mammalian cells was tested using HEK293, and the hemolysis activity was also investigated on human blood. Finally, synergistic studies were performed with four conventional antibiotics against four resistant strains of Gram-positive and Gram-negative bacteria. Results: The new peptide B1 exhibited broad-spectrum activities against all tested strains. The concentration against planktonic cells ranged between 10 and 20 μM. However, 40–60 μM were needed to eradicate the biofilms. B1 showed reduced toxicity toward mammalian cells with minimal hemolysis risk. On the other hand, the synergistic studies showed improved activities for the combined conventional antibiotics with a huge reduction in their minimum inhibitory concentration values. The concentrations of B1 peptide combined with the tested antibiotics were also decreased markedly down to 0.5 μM in some cases. Conclusion: B1 is a hybrid peptide from two cathelicidin peptides. It showed an improved activity compared to parent peptides. The hybridization was successful in this study. It generated a new potent broad-spectrum antimicrobial. The toxicity profile was improved, and the synergism with the convention antibiotics showed promising results.

Antimicrobial agents are one of the most widely used drugs in medicine. In the last fifty years, the misuse of these agents caused the emergence of resistant strains of bacteria that led to an increase in life-threatening infections. The need to develop new agents has become a priority, and antimicrobial peptides attained high consideration. The antimicrobial activities of a novel In-house designed hybrid cationic peptide (BKR1) were studied against different strains of Gram-negative bacteria. This was done using the broth dilution method as outlined by the Clinical and Laboratory Institute (CLSI). Checkerboard assy was employed to investigate the synergistic activity of BKR1 peptide with four antibiotics (Levofloxacin, chloramphenicol, rifampicin, and ampicillin). Finally, the cytotoxicity of BKR1 was evaluated against human blood cells and mammalian kidney cells (Vero cells). BKR1 displayed bactericidal activity against tested strains of Gram-negative bacteria, with zero hemolytic effects. It also acts as a strong adjuvant with levofloxacin, chloramphenicol, and rifampicin against resistant strains of P. aeruginosa and E. coli. This study represents the design and elucidation of the antimicrobial activities of a novel hybrid antimicrobial peptide named (BKR1). Our results indicate thar BKR1 is a promising candidate to treat resistant infectious diseases individually or as an adjuvant with conventional antibiotics.

Notable emergence of multidrug-resistant bacteria has become increasingly problematic worldwide. Most patients with cystic fibrosis (CF) suffer from chronic persistent infections with frequent occu...

The growing microbial resistance to antibiotics is a global public concern, which creates serious needs for newer antimicrobial agents. Antimicrobial peptides (AMPs) are increasingly exploited in drug development as therapeutic candidates. Here, we aimed to design and characterize a novel peptide with broad spectrum antimicrobial activity. Hybridization and sequence modification approaches were used to design the novel peptide, named HAZ, aiming at optimizing the physicochemical parameters involved in antimicrobial activity. Peptide activities were assessed alone or combined with different selected antibiotics against various sensitive and drug-resistant bacterial strains. In addition, the hemolysis and the cytotoxic activities of HAZ peptide were evaluated on human red blood cells and epithelial adenocarcinoma cells (A549), respectively. HAZ peptide was sequentially modified to result in favored physicochemical parameters (helicity 95.24 %, hydrophobic ratio 47 %, and net charge of 8 + ). Functional assessment of HAZ revealed significant antimicrobial activity, with MIC values of 15 – 20 µM against tested bacterial strains. It also exhibited biofilm eradication activity at slightly higher concentrations. HAZ-antibiotics combinations exhibited a synergistic action mode that led to dramatic decrease in the MIC values for both HAZ peptide and the antibiotic. Such efficacy was accompanied with minimal hemolytic toxicity on human erythrocytes. Importantly, HAZ displayed promising anticancer activity against human lung cancer cells. Rationally-designed antimicrobial peptides offer promising alternatives to the current antibiotics for management of infectious diseases. HAZ peptide is a broad-spectrum AMP, and a promising candidate for antimicrobial and anticancer drug development.