Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou, 570228, China; Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, 570311, China.
Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou, 570228, China.
Microb Pathog. 2023 Dec;185:106447. doi: 10.1016/j.micpath.2023.106447. Epub 2023 Nov 14.
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.
李斯特菌是一种食源性病原体，可导致李斯特菌病，死亡率很高，其耐药性（MDR）众所周知且呈逐渐上升趋势。因此，人们迫切需要寻找替代抗菌策略来治疗这种知名病原体。抗生物膜和抗毒力策略正在被探索作为治疗细菌感染的新方法。在这项研究中，从链霉菌中分离出一种名为鞘脂霉素的罕见抗菌物质，其对李斯特菌具有很强的抗菌活性。接下来，在亚最小抑菌浓度（sub-MICs）下单独或联合使用链霉素和阿米卡星研究鞘脂霉素对李斯特菌生物膜形成和溶血素 O（LLO）产生的抑制作用。结晶紫染色证实，鞘脂霉素与链霉素或阿米卡星联合使用可以在亚 MIC 下显著减少李斯特菌的生物膜形成，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，亚 MIC 的鞘脂霉素可以显著抑制 LLO 的分泌。此外，鞘脂霉素在亚 MIC 下可以抑制与生物膜和主要毒力因子（如 LLO、鞭毛和金属蛋白酶）相关的基因转录。因此，该研究深入了解了鞘脂霉素作为一种替代抗菌剂来对抗李斯特菌。
