Temporin-GHa (GHa) peptide

The abuse of antibiotics has led to the emergence of multidrug-resistant bacteria, which isbecoming a serious worldwide problem people have to face. In our previous study, temporin-GHa(GHa) cloned from Hylarana guentheri showed antimicrobial activity against Gram-positive bacteria.In order to improve its therapeutic potential, we used a template-based and a database-assisteddesign to obtain three derived peptides by replacing the histidine at both ends of GHa with lysine,which exhibited faster and stronger bactericidal activity and a broader spectrum than the parentpeptide. GHaK and GHa4K targeted to the bacterial membrane to exert their antibacterial activitiesat a faster membrane damage rate. The derived peptides inhibited the initial adhesion and theformation of Staphylococcus aureus biofilms, and eradicated the mature biofilms, which indicated thatthe derived peptides effectively penetrated the biofilm and killed bacteria. The therapeutic index (TI)and cell selectivity index (CSI) of the derived peptides increased significantly, which means a broadertherapeutic window of the derived peptides. The derived peptides with improved activity and cellselectivity have the potential to be the promising candidates for the treatment of S. aureus infections.Our research also provides new insights into the design and development of antimicrobial peptides.