Li Songryong, Liu Gaomin, Kang Jongguk, Li Zhongjie, Cao Zhijian
State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, 430072, China; Center for BioDrug Research, Wuhan University, Wuhan, 430072, China; Faculty of Life Science, Kim Hyong Jik University of Education, Pyongyang, Democratic People's Republic of Korea.
State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, 430072, China.
Toxicon. 2023 Aug 1;231:107189. doi: 10.1016/j.toxicon.2023.107189. Epub 2023 Jun 7.
Antimicrobial peptides (AMPs) are a new type of antibiotic and target a variety of microbes, including antibiotic-resistant strains; thus, AMPs have attracted widespread interest. Scorpion venoms contain many bioactive peptides, including AMPs, and have become an important natural resource of peptide-based drugs. Here, the antibacterial peptide gene Hp1470 from the venom of the scorpion Heterometrus petersii was characterized, and its antibacterial activity was determined. The cDNA sequence of Hp1470 is 300 nt in length and contains an open reading frame (ORF) of 207 nt. The ORF was shown to encode 68 amino acid residues, including a signal peptide (23 aa), a mature peptide (13 aa), a C-terminal posttranslational processing signal (3 aa), and a propeptide (29 aa). Multiple sequence alignment results indicated that Hp1470 is an antibacterial peptide. The mature peptide Hp1470, which has a molecular mass of 1564.09 Da, was further chemically synthesized with a purity of greater than 95%. Antimicrobial assays showed that the synthesized Hp1470 exerted an inhibitory effect on Gram-positive bacteria and clinical drug-resistant strains, including PRSA and MRSA, but not Gram-negative bacteria. Hp1470 was further found to protect mice from MRSA infection, suggesting its potential application as an in vivo antimicrobial agent. Interestingly, Hp1470 only inhibited bacterial growth but did not kill bacteria, which was consistent with scanning electron microscopy results showing that Hp1470 did not lyse the cell membrane of Staphylococcus aureus. Our work provides a new direction for developing antibacterial agents with different modes of action from natural scorpion venoms.
抗菌肽（AMPs）是一种新型抗生素，可靶向多种微生物，包括耐药菌株；因此，抗菌肽已引起广泛关注。蝎毒含有许多生物活性肽，包括抗菌肽，已成为基于肽的药物的重要天然资源。在此，对彼得异蝎毒液中的抗菌肽基因Hp1470进行了表征，并测定了其抗菌活性。Hp1470的cDNA序列长度为300 nt，包含一个207 nt的开放阅读框（ORF）。该ORF编码68个氨基酸残基，包括一个信号肽（23个氨基酸）、一个成熟肽（13个氨基酸）、一个C端翻译后加工信号（3个氨基酸）和一个前肽（29个氨基酸）。多序列比对结果表明Hp1470是一种抗菌肽。进一步化学合成了分子量为1564.09 Da、纯度大于95%的成熟肽Hp1470。抗菌试验表明，合成的Hp1470对革兰氏阳性菌和临床耐药菌株（包括PRSA和MRSA）有抑制作用，但对革兰氏阴性菌无抑制作用。进一步发现Hp1470可保护小鼠免受MRSA感染，表明其作为体内抗菌剂的潜在应用价值。有趣的是，Hp1470仅抑制细菌生长但不杀死细菌，这与扫描电子显微镜结果一致，即Hp1470不会裂解金黄色葡萄球菌的细胞膜。我们的工作为开发具有与天然蝎毒不同作用方式的抗菌剂提供了新方向。
