Key Laboratory of New Animal Drug Project of Gansu Province, Key Laboratory of Veterinary Pharmaceutical Development of Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Sciences, Lanzhou 730050, China.
Int J Mol Sci. 2024 Jan 23;25(3):1397. doi: 10.3390/ijms25031397.
() exhibits the ability to form biofilms as a means of adapting to its adverse surroundings. in this biofilm state demonstrates remarkable resistance, evades immune system attacks, and poses challenges for complete eradication, thereby complicating clinical anti-infection efforts. Moreover, the precise mechanisms governing biofilm formation and disruption remain elusive. Recent studies have discovered that fingolimod (FLD) exhibits biofilm properties against Gram-positive bacteria. Therefore, the antibiofilm properties of FLD were evaluated against multidrug-resistant (MDR) in this study. The antibiofilm activity of FLD against was assessed utilizing the Alamar Blue assay along with confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM), and crystal violet (CV) staining. The results showed that FLD effectively reduced biofilm formation, exopolysaccharide (EPS), motility, and bacterial abundance within biofilms without impeding its growth and metabolic activity. Furthermore, the inhibitory impact of FLD on the production of autoinducer-2 (AI-2) signaling molecules was identified, thereby demonstrating its notable anti-quorum sensing (QS) properties. The results of qRT-PCR analysis demonstrated that FLD significantly decreased the expression of genes associated with the efflux pump gene (, , , , and ), outer membrane (OM) porin proteins (, ), the quorum-sensing (QS) system (), lipopolysaccharide (LPS) production (), and EPS production (). Simultaneously, FLD exhibited evident antibacterial synergism, leading to an increased survival rate of infected with MDR . These findings suggested that FLD has substantial antibiofilm properties and synergistic antibacterial potential for colistin in treating infections.
（）能够形成生物膜，以此适应其不利的周围环境。处于生物膜状态的 表现出显著的抵抗力，能够逃避免疫系统的攻击，并且难以被彻底清除，这使得临床抗感染工作变得更加复杂。此外，生物膜形成和破坏的确切机制仍然难以捉摸。最近的研究发现，芬戈莫德（FLD）对革兰氏阳性菌具有生物膜特性。因此，本研究评估了 FLD 对多药耐药（MDR） 的抗生物膜特性。通过 Alamar Blue 测定法以及共聚焦激光扫描显微镜（CLSM）、扫描电子显微镜（SEM）和结晶紫（CV）染色评估 FLD 对 的抗生物膜活性。结果表明，FLD 可有效降低生物膜形成、胞外多糖（EPS）、运动性和生物膜内 的细菌丰度，而不会阻碍其生长和代谢活性。此外，还确定了 FLD 对自动诱导物-2（AI-2）信号分子产生的抑制作用，从而证明其具有显著的抗群体感应（QS）特性。qRT-PCR 分析结果表明，FLD 显著降低了与外排泵基因（、、、和）、外膜（OM）孔蛋白（、）、群体感应（QS）系统（）、脂多糖（LPS）产生（）和 EPS 产生（）相关的基因表达。同时，FLD 表现出明显的抗菌协同作用，导致感染 MDR 的 存活率提高了 。这些发现表明，FLD 具有显著的抗生物膜特性和协同抗菌潜力，可与多粘菌素联合用于治疗 感染。
