Antibacterial peptide BMAP-27

BMAP-27, a member of cathelicidin family, plays an important role against microorganisms, including bacteria and fungi. BMAP-27 may exert antimicrobial effects through membrane integrity disruption, but the exact molecular mechanism remains unclear. To identify the structural features important for antimicrobial activity and propose a mechanism underlying antibacterial effects, we determined the nuclear magnetic resonance structure of BMAP-27 in a membrane-mimetic environment and investigated its interactions with lipid membranes. BMAP-27 exhibited a long N-terminal α-helix with faces patterned into aromatic and cationic regions, central kink, and short hydrophobic C-terminal helix. While the N-terminal 18-residue peptide (BMAP-18) exerted only antibacterial activity, BMAP-27 showed potent activity against bacteria and cancer cells. Both peptides inhibited bacterial growth, but BMAP-18 showed delayed bactericidal activity and BMAP-27 completely killed bacteria within 20 min. The differences in antimicrobial activities and microbicidal kinetics may be associated with membrane permeabilisation; BMAP-27 rapidly and largely disrupted membrane integrity, whereas BMAP-18 showed low membrane disruption activity. Thus, the N-terminal helix is sufficient to inhibit bacterial growth and the C-terminal helix is involved in membrane permeabilisation for rapid bactericidal and efficient anticancer activities. The structural and functional characterisation of BMAP-27 may encourage the development of novel antimicrobial/anticancer agents.

Background: Antibiotic-resistant is considered one of the critical health challenges in the management of infectious diseases. Resistant bacterial strains to the different types of antibacterial agents have been spread worldwide. Anti-microbial peptides (AMPs), also called host defense peptides, have a broad spectrum of activity and targeting even to multi-drug resistant (MDR) bacteria, therefore, extensively studied, and developed as novel therapeutic antibacterial agents. Objectives: To design a novel SK4 hybrid peptide with improved characteristics compared with the BMAP-27 and Cecropin-A natural parents' peptides. Methods: The bioinformatic analysis of the SK4 peptide in comparison with the parents BMAP-27 and Cecropin-A peptides was conducted and it was fully characterized using specialized software. The antimicrobial and the antibiofilm activity of SK4 was tested, followed by a synergistic study with five conventional antibiotics (Levofloxacin, Rifampicin, Chloramphenicol, Doxycycline, and Ampicillin). Finally, the cytotoxicity against horse erythrocytes and mammalian cells was assessed. Results: The SK4 peptide demonstrated broad-spectrum antimicrobial activity against both gram-positive and gram-negative bacteria. The peptide also did not show any hemolytic activity even when used at concentrations ten folds higher than its MICs value. The SK4 peptide also showed a synergistic mode of action when combined with antibiotics that resulted in a significant decrease in MIC values for both the peptide and the antibiotics. Conclusions: The SK4 peptide showed better activity, selectivity, and safety profile than the parent peptides, making it a novel potential treatment for MDR bacterial infections.

Background & objective: The spread and development of drug-resistant bacterial strains has prompted the hunt for novel antibacterial polypeptides undergoing conformational changes to confer rapid bactericidal effects. The aim of this study was to evaluate the effect of novel BMAP27-Melittin conjugated peptide- nanoparticle (NP) against Streptococcus mutans as the primary pathogen from subgingival plaques. Methods: Sixty subgingival plaque samples were collected, and 39 S. mutans isolates were identified. The BMAP27-Melittin conjugated peptide was purchased from GenScript Company, USA. Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC), Biofilm Inhibitory Concentration (BIC), and Biofilm Eradication Concentration (BEC) of BMAP27-Melittin-NP were calculated using the microtiter method. Results: Thirty-nine infected subjects were reported, including 24 males and 15 females (P=0.299). MIC, MBC, BIC, and BEC of BMAP27-Melittin-NP against S. mutans were 1.8, 2.9, 2.1, and 3.8μg/mL, respectively. The mean MBC, BEC, and BIC values were significantly lower among clinical isolates than S. mutans ATCC 35688 standard strain (P=0.032, 0.001, and 0.001, respectively). Conclusion: BMAP27-Melittin-NP demonstrated significant antibacterial and anti-biofilm effects against clinical isolates of S. mutans which can be considered a promising compound to prevent or treat dental caries and eradicate the oral infections.