Abstract
The abuse of antibiotics has led to the emergence of multidrug-resistant bacteria, which is becoming 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-assisted design 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 parent peptide. GHaK and GHa4K targeted to the bacterial membrane to exert their antibacterial activities at a faster membrane damage rate. The derived peptides inhibited the initial adhesion and the formation of Staphylococcus aureus biofilms, and eradicated the mature biofilms, which indicated that the 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 broader therapeutic window of the derived peptides. The derived peptides with improved activity and cell selectivity 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.
Highlights
Infectious diseases have been one of the most life-threatening health problems worldwide throughout human history
More and more natural and designed antimicrobial peptides (AMPs) have been reported, and various antimicrobial peptide databases have emerged in the era of big data, providing researchers with very convenient and powerful tools to learn more about the AMPs
Physicochemical properties of those four peptides are consistent with the common properties of AMPs (Table 1), indirectly indicating that they may have antimicrobial activity
Summary
Infectious diseases have been one of the most life-threatening health problems worldwide throughout human history. The discovery of antibiotics lit up the dawn light to people who suffered from infections and saved their lives, making antibiotics the ultimate weapon against bacteria. Due to the misuse of conventional antibiotics, bacteria have developed various strategies to avoid the killing efficacy of antibiotics [1]. Bacteria have accelerated their adaptation steps to resist antibiotics, developing multidrug-resistance to more antibiotic classes. Staphylococcus aureus is a symbiotic bacterium of humans, distributed in the skin, nose, respiratory tract, and digestive system, which is the main pathogen causing skin and respiratory infections [4,5]. S. aureus infections can be treated with some antibiotics, including penicillin, oxacillin, or vancomycin, but the multidrug-resistant bacteria, like methicillin-resistant (MRSA) and vancomycin-resistant strains (VRSA), are very difficult to treat, leading to serious infections in hospital [6,7]
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