Temporin-GHb-Derived Peptides Exhibit Potent Antibacterial and Antibiofilm Activities against Staphylococcus aureus In Vitro and Protect Mice from Acute Infectious Pneumonia

• DOI: 10.1021/acsinfecdis.2c00544
• Publication Date: 2023-03-02T14:44:30Z
• Authors: Xiao Jin; Xuanyu Hu; Shangjun Jiang; Ting Zhao; Yanmei Zha; Shuangshuang Wei; Jianguo Zhao; Manchuriga Wang; Yingxia Zhang
• Keywords: Minimum bactericidal concentration

With the continuous development of drug resistance in bacteria to traditional antibiotics, demand for novel antibacterial agents is urgent. Antimicrobial peptides (AMPs) are promising candidates because their unique mechanism action and low tendency induce resistance. Previously, we cloned temporin-GHb (hereafter referred simply as "GHb") from Hylarana guentheri. In this study, a series derived were designed, namely, GHbR, GHbK, GHb3K, GHb11K, GHbK4R. The five had stronger activities against Staphylococcus aureus than parent peptide GHb could effectively inhibit formation biofilms eradicate mature vitro. GHbK4R exerted bactericidal effects by disrupting membrane integrity. However, GHb11K exhibited bacteriostatic efficacy with toroidal pore on cell membrane. comparison GHbK4R, GHb3K showed much lower cytotoxicity A549 alveolar epithelial cells, an IC50 > 200 μM, which was higher its minimal inhibitory concentration (MIC = 3.1 μM) S. aureus. anti-infection potential investigated vivo. Compared vancomycin, two displayed significant mouse model acute pneumonia infected Both also no obvious toxicity normal mice after intraperitoneal administration (15 mg/kg) 8 days. Our results indicate that might be treatment bacterial