Engineered probiotic Lactobacillus plantarum WCSF I for monitoring and treatment of Staphylococcus aureus infection

作者：Haoran Li, Minjun Jia, Qingsheng Qi, Qian Wang · 发表于：Microbiology Spectrum · 年份：2023 · DOI：10.1128/spectrum.01829-23 · 被引用次数：25 · 研究领域：Antimicrobial Peptides and Activities、Biochemical and Structural Characterization、Antimicrobial Resistance in Staphylococcus

ABSTRACT Lactobacillus plantarum is one of the most thoroughly researched species of the genus Lactobacillus , which possesses the characteristics of easy genetic transformation, high-density growth, and high intestinal tract survival. L. plantarum has been proven to play a potential role as a probiotic delivery vector. Staphylococcus aureus is a common Gram-positive pathogenic bacterium. It uses an autoinducer peptide (AIP) produced by its Agr quorum-sensing (AgrQS) system to sense the population density. Using the quorum-sensing mechanism exclusive to S. aureus , we constructed an AgrQS system in L. plantarum WCSF induction and killing modules based on AIP sensing and regulation so that L. plantarum could effectively eliminate S. aureus when detecting exogenous AIP at nanomolar concentrations. By optimizing the expression strength of the two-component system AgrAC using different L. plantarum -derived promoters and replacing the core promoter of the AgrA-activating promoter, the activation strength of AgrQS increased from the initial 1.2-fold to 5.3-fold. By introducing the signal peptide N20-guided lysostaphin aureus protein, engineered L. plantarum was able to effectively control the release of lysostaphin aureus protein and inhibit the growth of S. aureus . For the first time, engineered L. plantarum can detect and treat S. aureus infection, laying the groundwork for the future development of engineered probiotics for the monitoring and therapy of intestinal pathogens. I...