Li Jinqiao, Liang Yan, Su Minhong, Wu Jiena, Chai Jinwei, Xiong Weichen, Mo Guoxiang, Chen Xin, Xu Xueqing
Department of Pulmonary and Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China; Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
Department of Pulmonary and Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
Biochem Pharmacol. 2023 Apr;210:115471. doi: 10.1016/j.bcp.2023.115471. Epub 2023 Mar 7.
Septic shock caused by Gram-positive bacteria continues to be a major cause of morbidity and mortality in intensive care units globally. Most Temporins are excellent growth inhibitors of gram-positive bacteria and candidates for developing antimicrobial treatments due to their biological action and small molecular weight. In this study, a novel Temporin peptide from the skin of Fejervarya limnocharis frog, named as Temporin-FL, was characterized. Temporin-FL was found to adopt typical α-helical conformation in SDS solution and to exhibit selective antibacterial activity against Gram-positive bacteria through a membrane destruction mechanism. Accordingly, Temporin-FL showed protective effects against Staphylococcus aureus-induced sepsis in mice. Finally, Temporin-FL was demonstrated to exert anti-inflammatory effects by neutralizing the action of LPS/LTA and by inhibiting MAPK pathway activation. Therefore, Temporin-FL represents a novel candidate for moleculartherapy of Gram-positive bacterial sepsis.
革兰氏阳性菌引起的脓毒性休克仍然是全球重症监护病房发病和死亡的主要原因。由于其生物学作用和小分子量,大多数爪蟾抗菌肽是革兰氏阳性菌的优秀生长抑制剂,也是开发抗菌治疗药物的候选物。在本研究中,对一种从泽陆蛙皮肤中提取的新型爪蟾抗菌肽进行了表征,命名为Temporin-FL。研究发现,Temporin-FL在SDS溶液中呈现典型的α-螺旋构象,并通过膜破坏机制对革兰氏阳性菌表现出选择性抗菌活性。因此,Temporin-FL对小鼠金黄色葡萄球菌诱导的败血症具有保护作用。最后,研究证明Temporin-FL通过中和LPS/LTA的作用和抑制MAPK途径激活发挥抗炎作用。因此,Temporin-FL是革兰氏阳性菌败血症分子治疗的新候选物。