单核细胞增生李斯特菌（Listeria monocytogenes,LM）是典型的人畜共患食源性病原体，其耐药机制及抑制技术的研究对保障人畜安全具有重大意义。本课题以食源性多重耐药LM为对象，探讨SSRI类化合物对LM的抑制及多重耐药性逆转作用机理。在前期研究利用药敏检测SSRI类化合物体外抑制LM多种耐药株基础上，借助透射电镜等细胞学手段观测细胞膜表面三维形貌影响，通过测定胞内氧化指标，间接考察其对细胞膜代谢的影响；利用高通量测序技术分析其对LM转录组水平的影响，确定相关作用蛋白及其代谢途径，用λ-red重组系统敲除假设的耐药性作用基因，深入研究SSRI类化合物对LM多重耐药性的逆转作用机理，从基因水平探索出对人畜安全又能高效抑菌且逆转耐药活性的机制。在人畜受到多重耐药菌感染时，增加可选择的处理手段，为控制和解决微生物多重耐药问题提供理论依据和技术基础。

Novel antimicrobial drugs are lacking, however, so-called “non-antibiotics” may act as 19 antibiotics and/or add in restoring the antibiotic sensitivity of antibiotic resistant bacteria.Listeria monocytogenes (LM) is the main pathogen of zoonosis listerellosis. It is critical to investigate the mechanism and the method to control the antibiotic resistance of LM. In this study, we study the inhibitory effect and the mechanism of multidrug resistance reversal effect of selective serotonin reuptake inhibitors (SSRIs) on LM. The antibacterial activities andmultidrug resistance reversal activities of SSRIs are detected by drug susceptibility test. The effect of SSRIs on the three-dimensional morphology ofthe surface of LM cell membrane is observed by means of cell biology, such as transmission electron microscopy, and the indirect influence on the cell membraneis measured by intracellular oxidation indexes. The influence of SSRIs on thelevel of LM transcriptome is analyzed by high-throughput sequencing technology.Further, the related protein and metabolic pathways are determined. Finally, wefurther analyze themechanism of multidrug resistance reversal of SSRIs on LM by main related gene knockout with lambda - red restructuring system. The aim of thisstudy is to explore the mechanism of antibacterial and drug resistance reversalactivities of this kind of the compounds from gene level, which is safe to peopleand animal and also with high efficiency. This study will provide theoreticalbasis and technical basis for generating more choices of treatment methods in caseof people or animals infected with multidrug-resistant bacteria, forscientifically application of antibiotics in animal husbandry and microecology,and to control and solve the problem of multi-drug resistance of microorganisms.