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蛛形纲毒液中的抗菌肽及其在商业抗生素存在下的杀菌活性。

Antimicrobial peptides from arachnid venoms and their microbicidal activity in the presence of commercial antibiotics.

机构信息

Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Apartado Postal 510-3, Cuernavaca Mor, México.

出版信息

J Antibiot (Tokyo). 2013 Jan;66(1):3-10. doi: 10.1038/ja.2012.87. Epub 2012 Oct 24.

DOI:10.1038/ja.2012.87
PMID:23093034
Abstract

Two antimicrobial peptides (AMPs), named La47 and Css54, were isolated from the venom of the spider Lachesana sp. and from the scorpion Centruroides suffusus suffusus, respectively. The primary structures of both La47 and Css54 were determined using N-terminal sequencing and mass spectrometry. La47 is identical to the AMP latarcin 3a obtained previously from the venom of the spider Lachesana tarabaevi, but the primary structure of Css54 is unique having 60% identities to the AMP ponericin-W2 from the venom of the ant Pachycondyla goeldii. Both La47 and Css54 have typical α-helix secondary structures in hydrophobic mimicking environments. The biological activities of both La47 and Css54 were compared with the AMP Pin2 isolated from the venom of the scorpion Pandinus imperator. La47 has lower antimicrobial and hemolytic activities compared with Css54 and Pin2. In addition, La47 and Pin2 were evaluated in the presence of the commercial antibiotics, chloramphenicol, ampicillin, novobiocin, streptomycin and kanamycin. Interestingly, the best antimicrobial combinations were obtained with mixtures of La47 and Pin2 with the antibiotics chloramphenicol, streptomycin and kanamycin, respectively. Furthermore, the novel peptide Css54 was evaluated in the presence of antibiotics used for the treatment of tuberculosis, isoniazid, rifampicin, pyrazinamide and ethambutol. Although the mixtures of Css54 with isoniazid, pyrazinamide or ethambutol inhibit the growth of Staphylococcus aureus, the best effect was found with rifampicin. Overall, these data show a motivating outlook for potential clinical treatments of bacterial infections using AMPs and commercial antibiotics.

摘要

两种抗菌肽(AMPs),分别命名为 La47 和 Css54,从蜘蛛 Lachesana sp. 的毒液和蝎子 Centruroides suffusus suffusus 的毒液中分离得到。使用 N 端测序和质谱法确定了 La47 和 Css54 的一级结构。La47 与之前从蜘蛛 Lachesana tarabaevi 毒液中获得的 AMP latarcin 3a 相同,但 Css54 的一级结构是独特的,与来自蚂蚁 Pachycondyla goeldii 毒液的 AMP ponericin-W2 有 60%的同源性。La47 和 Css54 在疏水环境中都具有典型的α-螺旋二级结构。比较了 La47 和 Css54 与从蝎子 Pandinus imperator 毒液中分离得到的 AMP Pin2 的生物学活性。与 Css54 和 Pin2 相比,La47 的抗菌和溶血活性较低。此外,在存在商业抗生素氯霉素、氨苄西林、新生霉素、链霉素和卡那霉素的情况下,评估了 La47 和 Pin2 的活性。有趣的是,与抗生素氯霉素、链霉素和卡那霉素分别组合使用时,获得了最佳的抗菌组合。此外,还评估了新型肽 Css54 在用于治疗结核病的抗生素异烟肼、利福平、吡嗪酰胺和乙胺丁醇存在下的活性。尽管 Css54 与异烟肼、吡嗪酰胺或乙胺丁醇的混合物抑制金黄色葡萄球菌的生长,但与利福平的效果最好。总的来说,这些数据显示了使用 AMPs 和商业抗生素治疗细菌感染的潜在临床治疗的令人鼓舞的前景。

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