State Key Laboratory of Marine Environmental Science, College of Ocean and Earth Sciences, Xiamen University, Xiamen, China.
State-Province Joint Engineering Laboratory of Marine Bioproducts and Technology, College of Ocean and Earth Sciences, College of Ocean and Earth Sciences, Xiamen University, Xiamen, China.
Front Cell Infect Microbiol. 2022 Aug 2;12:928220. doi: 10.3389/fcimb.2022.928220. eCollection 2022.
Antimicrobial peptides (AMPs) may be the most promising substitute for antibiotics due to their effective bactericidal activity and multiple antimicrobial modes against pathogenic bacteria. In this study, a new functional gene named was identified in , which encoded 216 amino acids of mature peptide. , Spgillcin was dominantly expressed in the gills of male and female crabs, offering the highest expression level among all tested organs or tissues. The expression pattern of Spgillcin was significantly altered when challenged by , indicating a positive immune response. , a functional truncated peptide Spgillcin derived from the amino acid sequence of Spgillcin was synthesized and showed a broad-spectrum and potent antibacterial activity against several bacterial strains, including the clinical isolates of multidrug-resistant (MDR) strains, with a range of minimum inhibitory concentrations from 1.5 to 48 μM. Spgillcin also showed rapid bactericidal kinetics for and but did not display any cytotoxicity to mammalian cells and maintained its antimicrobial activity in different conditions. Mechanistic studies indicated that Spgillcin was mainly involved in the disruption of cell membrane integrity where the membrane components lipoteichoic acid and lipopolysaccharide could significantly inhibit the antimicrobial activity in a dose-dependent manner. In addition, Spgillcin could change the membrane permeability and cause the accumulation of intracellular reactive oxygen species. No resistance was generated to Spgillcin when the clinical isolates of methicillin-resistant and MDR were treated with Spgillcin and then subjected to a long term of continuous culturing for 50 days. In addition, Spgillcin exerted a strong anti-biofilm activity by inhibiting biofilm formation and was also effective at killing extracellular in the cultural supernatant of RAW 264.7 cells. Taken together, Spgillcin has strong potential as a substitute for antibiotics in future aquaculture and medical applications.
抗菌肽(AMPs)可能是抗生素最有前途的替代品,因为它们具有有效的杀菌活性和针对致病菌的多种抗菌模式。在这项研究中,在 中鉴定出一个名为 的新功能基因,该基因编码 216 个成熟肽的氨基酸。 ,Spgillcin 在雌雄蟹的鳃中表达占优势,在所有测试的器官或组织中表达水平最高。当受到 刺激时,Spgillcin 的表达模式发生明显变化,表明存在正向免疫反应。 ,一种源自 Spgillcin 氨基酸序列的功能截断肽 Spgillcin 被合成并表现出对多种细菌菌株的广谱和强效抗菌活性,包括临床分离的多药耐药(MDR)菌株,其最小抑菌浓度范围从 1.5 到 48 μM。Spgillcin 对 和 也表现出快速杀菌动力学,但对哺乳动物细胞没有任何细胞毒性,并在不同条件下保持其抗菌活性。机制研究表明,Spgillcin 主要参与破坏细胞膜完整性,其中膜成分脂磷壁酸和脂多糖可以以剂量依赖的方式显著抑制其抗菌活性。此外,Spgillcin 可以改变膜通透性并导致细胞内活性氧物质的积累。当用 Spgillcin 处理耐甲氧西林的 和 MDR 临床分离株并随后进行长达 50 天的连续培养时,未对 Spgillcin 产生耐药性。此外,Spgillcin 通过抑制生物膜形成表现出强大的抗生物膜活性,并且在 RAW 264.7 细胞的培养上清液中对细胞外 也有效。总之,Spgillcin 在未来的水产养殖和医学应用中具有替代抗生素的强大潜力。