School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, Korea.
Department of Agricultural Biology, National Academy of Agricultural Science, RDA, Wanju, Republic of Korea.
J Appl Microbiol. 2020 Aug;129(2):287-295. doi: 10.1111/jam.14632. Epub 2020 Mar 22.
Emergence and rapid dissemination of antibiotic-resistant bacteria is becoming a severe problem to public health. The search for antimicrobial substitutes for antibiotics is necessary. Lactoferricin B like peptide (LBLP) is a 23-mer antimicrobial peptide (AMP), derived from the big centipede Scolopendra subspinipes mutilans. Although its antifungal effect and its mechanism have been reported, the antibacterial activity has not yet been elucidated.
In this study, we investigated antibacterial activity of LBLP and its mode of action. LBLP showed potent antibacterial effect against pathogenic bacteria Escherichia coli and did not show haemolytic activity against human erythrocyte. The general antimicrobial mechanism of AMP is to disrupt the cell membrane, however, LBLP exerted its antibacterial activity by causing apoptosis-like death through reactive oxygen species (ROS) generation. LBLP-treated E. coli cells exhibited hallmarks of apoptosis, such as membrane depolarization, DNA fragmentation, caspase-like protein activation and phosphatidylserine exposure. These apoptotic features were attenuated by pretreatment of NAC, a representative ROS scavenger.
These results demonstrate that LBLP exerted its antibacterial activity by generating ROS and inducing apoptosis-like death in E. coli. LBLP is not membrane destructive per se, but essentially a metabolic inhibitor.
Lactoferricin B like peptide is potential candidate to replace conventional antibiotics that are less effective because of its unique properties.
抗生素耐药菌的出现和快速传播正成为公共卫生的严重问题。因此，有必要寻找抗生素的替代品。乳铁蛋白衍生抗菌肽（LBLP）是一种 23 肽抗菌肽（AMP），来源于少棘蜈蚣。虽然已经报道了其抗真菌作用及其机制，但抗菌活性尚未阐明。
在本研究中，我们研究了 LBLP 的抗菌活性及其作用机制。LBLP 对致病性细菌大肠杆菌表现出很强的抗菌作用，对人红细胞没有溶血活性。AMP 的一般抗菌机制是破坏细胞膜，然而，LBLP 通过生成活性氧（ROS）诱导细胞发生类似于凋亡的死亡来发挥其抗菌活性。用 LBLP 处理的大肠杆菌细胞表现出类似于凋亡的特征，如膜去极化、DNA 片段化、半胱天冬酶样蛋白激活和磷脂酰丝氨酸暴露。NAC（一种代表性的 ROS 清除剂）预处理可减轻这些凋亡特征。
这些结果表明，LBLP 通过产生 ROS 并诱导大肠杆菌发生类似于凋亡的死亡来发挥其抗菌活性。LBLP 本身不是破坏膜的物质，而是一种代谢抑制剂。
乳铁蛋白衍生抗菌肽因其独特的性质可能成为替代传统抗生素的潜在候选药物，因为传统抗生素的效果较差。
