The First Lanthipeptide from Lactobacillus iners, Inecin L, Exerts High Antimicrobial Activity against Human Vaginal Pathogens
The First Lanthipeptide from Lactobacillus iners, Inecin L, Exerts High Antimicrobial Activity against Human Vaginal Pathogens
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第一个来自惰性乳杆菌的羊毛硫肽，inecin L，对人类阴道病原体具有高抗菌活性
DOI：
10.1128/aem.02123-22
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发表时间：
2023-02-27
影响因子：
4.4
通讯作者：
Zhong, Jin
中科院分区：
文献类型：
--
作者：
Li, Lili;Zhang, Jie;Zhong, Jin
人类阴道微生物群在防止病原菌，真菌和病毒入侵方面起着至关重要的作用。阴道乳酸杆菌属优势菌群显示出巨大的益生菌开发潜力，阴道感染仍然是一个严重的公共卫生问题，开发新的方法来解决耐药病原体是一项紧迫的任务。主要的阴道乳杆菌物种及其活性代谢产物（例如，细菌素）具有击败病原体并帮助个体从疾病中恢复的潜力。在这里，我们第一次描述了一种新的lanthipeptide，inecin L，一种细菌素，来自于具有翻译后修饰的惰性乳杆菌。在阴道环境中，inecin L的生物合成基因被活跃地转录。Inecin L在纳摩尔浓度下对流行的阴道病原体如阴道加德纳菌和无乳链球菌具有活性。结果表明，inecin L的抗菌活性与其N端和带正电荷的His13残基密切相关。此外，inecin L是一种杀菌性羊毛硫肽，对细胞质膜几乎没有影响，但抑制细胞壁的生物合成。因此，本工作的特点是一种新的抗微生物羊毛硫肽从一个占主导地位的物种的人类阴道microbiots.IMPORTANCE人类阴道微生物群起着至关重要的作用，在防止病原菌，真菌和病毒入侵。阴道乳杆菌属的优势菌种显示出作为益生菌开发的巨大潜力。然而，参与益生菌特性的分子机制（如生物活性分子及其作用模式）仍有待确定。我们的工作描述了第一个羊毛硫肽分子从占主导地位的惰性乳杆菌。此外，inecin L是迄今为止在阴道乳杆菌中发现的唯一羊毛硫肽。Inecin L对常见的阴道致病菌和耐药菌株具有很强的抗菌活性，表明Inecin L是一种有效的抗菌分子。此外，我们的研究结果表明，inecin L具有特异性的抗菌活性，这与其N端和A环的残基有关，这将有助于lacticin 481类羊毛硫肽的构效关系研究。
The human vaginal microbiota plays essential roles in preventing pathogenic bacteria, fungi, and viruses from invading. The dominant vaginal Lactobacillus species show great potential to be developed as probiotics.Vaginal infections continue to be a serious public health issue, and developing new approaches to address antibiotic-resistant pathogens is an urgent task. The dominant vaginal Lactobacillus species and their active metabolites (e.g., bacteriocins) have the potential to defeat pathogens and help individuals recover from disorders. Here, we describe for the first time a novel lanthipeptide, inecin L, a bacteriocin from Lactobacillus iners with posttranslational modifications. The biosynthetic genes of inecin L were actively transcribed in the vaginal environment. Inecin L was active against the prevailing vaginal pathogens, such as Gardnerella vaginalis and Streptococcus agalactiae, at nanomolar concentrations. We demonstrated that the antibacterial activity of inecin L was closely related to the N terminus and the positively charged His13 residue. In addition, inecin L was a bactericidal lanthipeptide that showed little effect on the cytoplasmic membrane but inhibited the cell wall biosynthesis. Thus, the present work characterizes a new antimicrobial lanthipeptide from a predominant species of the human vaginal microbiota.IMPORTANCE The human vaginal microbiota plays essential roles in preventing pathogenic bacteria, fungi, and viruses from invading. The dominant vaginal Lactobacillus species show great potential to be developed as probiotics. However, the molecular mechanisms (such as bioactive molecules and their modes of action) involved in the probiotic properties remain to be determined. Our work describes the first lanthipeptide molecule from the dominant Lactobacillus iners. Additionally, inecin L is the only lanthipeptide found among the vaginal lactobacilli thus far. Inecin L shows strong antimicrobial activity toward the prevalent vaginal pathogens and antibiotic-resistant strains, suggesting that inecin L is a potent antibacterial molecule for drug development. In addition, our results show that inecin L exhibits specific antibacterial activity related to the residues in the N-terminal region and ring A, which will contribute to structure-activity relationship studies in lacticin 481-like lanthipeptides.