Jayathilaka E H T Thulshan, Rajapaksha Dinusha C, Nikapitiya Chamilani, Lee Joeun, De Zoysa Mahanama, Whang Ilson
College of Veterinary Medicine and Research Institute of Veterinary Medicine, Chungnam National University, Yuseong-gu, Daejeon 34134, Korea.
National Marine Biodiversity Institute of Korea (MABIK), 75, Jangsan-ro, 101beon-gil, Janghang-eup 33662, Korea.
Pharmaceuticals (Basel). 2022 Jul 27;15(8):928. doi: 10.3390/ph15080928.
Octoprohibitin is a synthetic antimicrobial peptide (AMP), derived from the prohibitin-2 gene of . It showed substantial activity against multidrug resistant (MDR) with a minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of 200 and 400 µg/mL, respectively. Time-kill kinetics and bacterial viability assays confirmed the concentration-dependent antibacterial activity of octoprohibitin against . The morphology and ultrastructure of were altered by treatment with octoprohibitin at the MIC and MBC levels. Furthermore, propidium iodide-fluorescein diacetate (PI-FDA) staining and 2',7'-dichlorodihydrofluorescein diacetate (HDCFDA) staining of octoprohibitin-treated revealed membrane permeability alterations and reactive oxygen species (ROS) generation, respectively. Agarose gel retardation results confirmed the DNA-binding ability of octoprohibitin to the genomic DNA of . Furthermore, octoprohibitin showed concentration-dependent inhibition of biofilm formation and eradication. The minimum biofilm inhibition concentration (MBIC) and minimum biofilm eradication concentration (MBEC) of octoprohibitin were 1000 and 1460 µg/mL, respectively. Octoprohibitin produced no significant cytotoxicity up to 800 µg/mL, and no hemolysis was observed up to 400 µg/mL. Furthermore, in vivo analysis in an -infected zebrafish model confirmed the effective bactericidal activity of octoprohibitin with higher cumulative survival percent (46.6%) and fewer pathological signs. Histological analysis showed reduced alterations in the gut, kidney, and gill tissues in the octoprohibitin-treated group compared with those in the phosphate-buffered saline (PBS)-treated group. In conclusion, our results suggest that octoprohibitin is a potential antibacterial and antibiofilm agent against MDR
八聚体抑制素是一种合成抗菌肽（AMP），源自[具体来源未提及]的抑制素-2基因。它对多重耐药菌（MDR）表现出显著活性，最小抑菌浓度（MIC）和最小杀菌浓度（MBC）分别为200和400µg/mL。时间杀菌动力学和细菌活力测定证实了八聚体抑制素对[具体细菌未提及]的浓度依赖性抗菌活性。在MIC和MBC水平用八聚体抑制素处理后，[具体细菌未提及]的形态和超微结构发生了改变。此外，八聚体抑制素处理的[具体细菌未提及]的碘化丙啶-荧光素二乙酸酯（PI-FDA）染色和2',7'-二氯二氢荧光素二乙酸酯（HDCFDA）染色分别显示了膜通透性改变和活性氧（ROS）生成。琼脂糖凝胶阻滞结果证实了八聚体抑制素与[具体细菌未提及]基因组DNA的DNA结合能力。此外，八聚体抑制素表现出浓度依赖性的生物膜形成抑制和根除作用。八聚体抑制素的最小生物膜抑制浓度（MBIC）和最小生物膜根除浓度（MBEC）分别为1000和1460µg/mL。八聚体抑制素在高达800µg/mL时未产生明显细胞毒性，在高达400µg/mL时未观察到溶血现象。此外，在[具体感染模型未提及]感染的斑马鱼模型中的体内分析证实了八聚体抑制素具有有效的杀菌活性，累积存活率更高（46.6%）且病理体征更少。组织学分析表明，与磷酸盐缓冲盐水（PBS）处理组相比，八聚体抑制素处理组的肠道、肾脏和鳃组织的改变减少。总之，我们的结果表明八聚体抑制素是一种针对多重耐药菌的潜在抗菌和抗生物膜剂
