Abstract：
Listeria monocytogenes, a foodborne pathogen that causes listeriosis with high fatality rate, exhibits multidrug resistance (MDR) known to be progressively increasing. Alternative antibacterial strategies are in high demand for treating this well-known pathogen. Anti-biofilm and anti-virulence strategies are being explored as novel approaches to treat bacterial infections. In this study, one rare antibacterial named setomimycin was isolated from Streptomyces cyaneochromogenes, which showed potent antibacterial activity against L. monocytogenes. Next, the inhibition of biofilm formation and listeriolysin O (LLO) production against L. monocytogenes were investigated at sub-minimal inhibitory concentrations (sub-MICs) of setomimycin alone or combined with kanamycin and amikacin. Crystal violet staining confirmed that setomimycin combining with kanamycin or amikacin could dramatically reduce biofilm formation against L. monocytogenes at sub-MICs, which was further evaluated by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). In the meantime, sub-MICs of setomimycin could significantly suppress the secretion of LLO. Furthermore, the transcription of genes associated with biofilms and main virulence factors, such as LLO, flagellum, and metalloprotease, were suppressed by setomimycin at sub-MICs. Hence, the study provided a deep insight into setomimycin as an alternative antibacterial agent against L. monocytogenes.
摘要：
单核细胞增生李斯特菌,一种食源性病原体，导致高致死率的李斯特菌病，表现出已知正在逐渐增加的多药耐药性(MDR)。替代的抗菌策略对于治疗这种众所周知的病原体有很高的需求。作为治疗细菌感染的新方法,正在探索抗生物膜和抗毒力策略。在这项研究中,一种罕见的抗菌药，名叫setomimycin，对单核细胞增生李斯特菌具有有效的抗菌活性。接下来,在亚最低抑制浓度（亚MIC）下，研究了单独或与卡那霉素和阿米卡星联合使用的结单霉素对单核细胞增生李斯特菌生物膜形成和李斯特菌溶血素O（LLO）产生的抑制作用。结晶紫染色证实，与卡那霉素或阿米卡星联合使用的塞托霉素可以显着减少亚MIC的单核细胞增生李斯特菌生物膜的形成，通过扫描电子显微镜（SEM）和共聚焦激光扫描显微镜（CLSM）进一步评估。同时,塞托霉素的亚MIC可以显着抑制LLO的分泌。此外，与生物膜和主要毒力因子相关的基因转录，比如LLO，鞭毛,和金属蛋白酶，在亚MIC时被塞托霉素抑制。因此，这项研究提供了一个深入的见解，以赛托霉素作为一种替代的抗菌剂对单核细胞增生李斯特菌。
