[1]梁东生,李焕影,许晓虎,等.抗变异链球菌多肽的设计、筛选及抗菌效果评价[J].南方医科大学学报,2019,(07):823.[doi:10.12122/j.issn.1673-4254.2019.07.12]
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抗变异链球菌多肽的设计、筛选及抗菌效果评价()
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《南方医科大学学报》[ISSN:1673-4254/CN:44-1627/R]

卷:
期数:
2019年07期
页码:
823
栏目:
出版日期:
2019-07-15

文章信息/Info

Title:
Design, screening and antimicrobial activity of novel peptides against Streptococcusmutans
作者:
梁东生李焕影许晓虎梁靖恒戴杏竹赵望泓
关键词:
抗菌肽龋病变异链球菌抗菌活性不完美两亲性
Keywords:
antimicrobial peptides dental caries Streptococcus mutans antimicrobial activity imperfect amphipathicity
DOI:
10.12122/j.issn.1673-4254.2019.07.12
摘要:
目的构建抗变异链球菌的低毒、高活性、快速的新型抗菌肽,并探讨其在防治龋病方面的潜能。方法根据两亲性正电性 α-螺旋结构抗菌肽的设计理念,对乳酸杆菌拮抗变异链球菌的代谢产物reuterin 6和/或gassericinA进行活性改造,分别通过细 菌敏感性实验、细胞毒性实验和杀菌-时效实验来评估衍生肽的抗菌效果和生物相容性,再进一步检测目标抗菌肽抗变异链球 菌的速率、抗多种口腔致病菌的活性和发展耐药菌株的能力。结果构建了6条AT-1衍生肽,并从中筛选出了低毒、高活性、快 速的新型抗菌肽AT-7;具有高疏水性、不完美两亲性的AT-7抑制变异链球菌、牙龈卟啉单胞菌和黏性放线菌等口腔致病菌的最 小抑菌浓度是3.3 μmol/L,在5 min内即可抑制88.7%的变异链球菌,以及连续诱导10代的处理仍不能产生耐AT-7的变异链球 菌。结论疏水性和不完美两亲性都是决定抗菌肽的抗菌效果的重要因素;抗菌肽AT-7具有转化为口腔临床用药的潜力。
Abstract:
Objective To construct antimicrobial peptides with potent antimicrobial activity, low cytotoxicity and efficient killing rate of Streptococcus mutans for prevention and treatment of dental caries. Methods We exploited the existing design strategies to modify reutericin 6 or gassericin A produced by Lactobacillus species in the oral cavity based on their cationicity, amphipathicity and α-helical structure. We examined their antimicrobial activities using bacterial susceptibility assay, their cytotoxicity through cytotoxicity assay and their killing rate of Streptococcus mutans with time-kill assay. We further evaluated the candidate derivatives for their killing rate against Streptococcus mutans, their antimicrobial activity against different oral pathogens and the development of drug resistance. Results We constructed 6 AT-1 derivatives, among which AT-7 showed an MIC of 3.3 μmol/L against Streptococcus mutans, Porphyromonas gingivalis and Actinomyces viscosus with a killing rate of 88.7% against Streptococcus mutans within 5 min. We did not obtain de novo strains of Streptococcus mutans resistant to AT- 7 after induction for 10 passages. Conclusion Hydrophobicity and imperfect amphipathic structure are two key parameters that define the antimicrobial potency of the antimicrobial peptides. The imperfectly amphipathic peptide AT-7 shows the potential for clinical application in dental caries treatment.

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更新日期/Last Update: 1900-01-01