在女性生殖道中，惰性乳杆菌是占主导地位的有益菌之一，而无乳链球菌是能引起严重感染的致病菌且具有广谱的耐药性。本研究首次从惰性乳杆菌基因组中发现了一种广泛存在的新型小肽（将其命名为inersin）的生物合成基因簇。不同于抗生素，inersin能显著降低无乳链球菌的致病性但几乎不影响其生长。这种作用方式新颖，且不易引发菌株的抗性。因此，本研究拟从新型小肽 inersin的生物合成途径，结构-活性关系和作用机制三方面开展工作，在阐明其生物合成关键基因或基因簇功能的基础上，建立其体外生物合成系统；结合定点突变和核磁共振等技术，解析inersin发挥“减毒”活性的结构基础；此外通过诱导活性检测以及蛋白-DNA相互作用等体内外研究，揭示inersin调控无乳链球菌双组份系统而抑制其致病性的分子机制。本研究将有助于阐明生殖道主导乳杆菌的益生机制，为抗感染药物或微生态制剂的研发提供理论指导。

Lactobacillus iners is a dominant species of beneficial bacteria in female reproductive tract, while Streptococcus agalactiae is a pathogen leading to serious invasive infections and it is resistant to a wild range of antibiotics. In this study, a biosynthetic cluster for a new type of peptide (named inersin), widely present in the genomes of L. iners, is first discovered. Different from antibiotics, inersin significantly reduces the pathogenicity of S. agalactiae but barely affects its growth. This novel mode of action of inersin also hardly triggers the resistance. Therefore, this study intends to work from the biosynthesis, structure-activity relationship and mechanism of action of inersin. Functions of the key biosynthetic genes or gene cluster will be determined. Based on that, the in vitro biosynthesis system for inersin will be constructed. Combining with the technique such as site-directed mutagenesis and nuclear magnetic resonance, the structural basis for the toxicity-attenuation activity of inersin will be resolved. In addition, the molecular mechanism of inersin to regulate the two-component system against the pathogenicity of S. agalactiae will be elucidated, by investigating reduction activity, and protein-DNA interaction and so on in vivo and in vitro. This work will be contributed to revealing the probiotic mechanism of the dominated species of vaginal Lactobacillus, and offering theoretical guidances for the development of anti-infection agents or probiotics.