Department of Microbiology, Faculty of Science, King Mongkut's University of Technology Thonburi (KMUTT), Bangkok, Thailand.
Theoretical and Computational Physics Group, Department of Physics, King Mongkut's University of Technology, Thonburi, (KMUTT), Thailand.
Curr Pharm Biotechnol. 2021;22(9):1216-1227. doi: 10.2174/1389201021666201020161428.
The consistently increasing reports of bacterial resistance and the reemergence of bacterial epidemics have inspired the health and scientific community to discover new molecules with antibacterial potential continuously. Frog-skin secretions constitute bioactive compounds essential for finding new biopharmaceuticals. The exact antibacterial characterization of dermaseptin related peptides derived from Agalychnis annae, is limited. The resemblance in their conserved and functionally linked genomes indicates an unprecedented opportunity to obtain novel bioactive compounds.
In this study, we derived a novel peptide sequence and determined its antibacterial potentials.
Consensus sequence strategy was used to design the novel and active antibacterial peptide named 'AGAAN' from skin secretions of Agalychnis annae. The in-vitro activities of the novel peptide against some bacterial strains were investigated. Time kill studies, DNA retardation, cytotoxicity, betagalactosidase, and molecular computational studies were conducted.
AGAAN inhibited P. aeruginosa, E. faecalis, and S. typhimurium at 20 μM concentration. E. coli and S. aureus were inhibited at 25 μM, and lastly, B. subtilis at 50 μM. Kinetics of inactivation against exponential and stationary growing bacteria was found to be rapid within 1-5 hours of peptide exposure, depending on time and concentration. The peptide displayed weak hemolytic activity between 0.01%-7.31% at the antibacterial concentrations. AGAAN efficiently induced bacterial membrane damage with subsequent cell lysis. The peptide's DNA binding shows that it also targets intracellular DNA by retarding its movement. Our in-silico molecular docking analysis displayed a strong affinity to the bacterial cytoplasmic membrane.
AGAAN exhibits potential antibacterial properties that could be used to combat bacterial resistance.
细菌耐药性的不断报告和细菌疫情的再次出现，促使卫生和科学界不断发现具有抗菌潜力的新分子。青蛙皮肤分泌物是发现新生物制药的必需生物活性化合物。来源于安娜氏树蛙的 Dermaseptin 相关肽的确切抗菌特性描述有限。它们保守且功能相关的基因组相似性表明，这是获得新型生物活性化合物的前所未有的机会。
在这项研究中，我们推导了一个新的肽序列，并确定了其抗菌潜力。
采用共识序列策略，从安娜氏树蛙皮肤分泌物中设计出一种新型活性抗菌肽，命名为“AGAAN”。研究了该新型肽对一些细菌菌株的体外活性。进行了时间杀伤研究、DNA 阻滞、细胞毒性、β-半乳糖苷酶和分子计算研究。
AGAAN 在 20 μM 浓度下抑制铜绿假单胞菌、粪肠球菌和鼠伤寒沙门氏菌。在 25 μM 时抑制大肠埃希菌和金黄色葡萄球菌，最后在 50 μM 时抑制枯草芽孢杆菌。发现对指数和静止生长细菌的灭活动力学在肽暴露后 1-5 小时内迅速发生，具体取决于时间和浓度。该肽在 0.01%-7.31%的抗菌浓度下显示出较弱的溶血活性。AGAAN 有效地诱导细菌膜损伤，随后导致细胞裂解。该肽的 DNA 结合表明，它还通过阻滞其运动来靶向细胞内 DNA。我们的计算机分子对接分析显示与细菌细胞质膜具有很强的亲和力。
AGAAN 具有潜在的抗菌特性，可用于对抗细菌耐药性。
