Title : Development of antimicrobial peptides… Rational design of SAMA and HAZ peptides
Abstract:
The rise in microbial resistance to antibiotics represents a significant global public health concern, underscoring the urgent need for novel antimicrobial agents. Antimicrobial peptides (AMPs) have emerged as promising candidates for therapeutic development. In this study, we designed and evaluated two novel AMPs, HAZ and SAMA, both exhibiting broad-spectrum antimicrobial activity. The HAZ peptide was developed using hybridization and sequence modification approaches to optimize its physicochemical properties, achieving a helicity of 95.24%, hydrophobic ratio of 47%, and a net charge of +8. HAZ demonstrated strong antimicrobial activity with minimum inhibitory concentrations (MICs) of 15–20 µM against both sensitive and drug-resistant bacterial strains, along with effective biofilm eradication at slightly higher concentrations. When combined with traditional antibiotics, HAZ exhibited a synergistic effect, significantly reducing the MIC values for both agents. Additionally, HAZ displayed low hemolytic toxicity on human erythrocytes and showed potential anticancer activity against human lung adenocarcinoma (A549) cells. The SAMA peptide, on the other hand, was designed by integrating segments from two naturally occurring peptides, brevinin-1E and bombolitin IV. SAMA exhibited potent and broad-spectrum antimicrobial effects against selected strains at concentrations of 5–15 µM and successfully eradicated biofilm-forming Gram-positive strains at 30–40 µM. Like HAZ, SAMA demonstrated synergistic or additive interactions when combined with traditional antibiotics, significantly reducing their required MICs. These results position HAZ and SAMA as rationally designed AMPs with significant potential for development as antimicrobial and anticancer therapies, offering a promising alternative to conventional antibiotics in the fight against infectious diseases.
