Lu Zhangping, Liang Xiaofang, Deng Wenbo, Liu Qianqian, Wang Yulin, Liu Meng, Lin Fugui, Liu Zhihong, Zhang Yu, Wang Wenjie, Sun Yingying, Wu Yaozhou, Wei Lianhua
Department of Clinical Laboratory, Gansu Provincial Hospital, Lanzhou, Gansu, China.
Front Cell Infect Microbiol. 2025 May 29;15:1552872. doi: 10.3389/fcimb.2025.1552872. eCollection 2025.
Methicillin-resistant (MRSA) poses a serious threat to the public health system due to its multi-drug resistance and strong biofilm-forming ability. Here, we explored the possible inhibitory mechanism of an antimicrobial peptide, Mastoparan X, against MRSA.
Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) of Mastoparan X against MRSA USA300 were determined by microbroth dilution method. The antibacterial activity of Mastoparan X against USA300 was then evaluated by time-growth curves, membrane fluidity, reactive oxygen species(ROS), flow cytometry, scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). In addition, the inhibitory and scavenging effects of Mastoparan X on USA300 biofilm were evaluated using crystal violet staining. Finally, gene expression changes in USA300 after treatment with Mastoparan X were analyzed by transcriptomics and verified by RT-qPCR.
The MIC and MBC of Mastoparan X on USA300 were 32 μg/mL and 64 μg/mL, respectively. SEM observation showed significant changes in cell morphology after Mastoparan X treatment. Flow cytometry confirmed that Mastoparan X promoted the apoptosis of MRSA cells. In addition, Mastoparan X inhibited the formation of MRSA biofilm while destroying the mature bioepithelia already formed. Transcriptomic analysis showed that 851 genes were significantly altered and ABC transport protein, amino acid biosynthesis, glycolysis and tricarboxylic acid (TCA) cycle were inhibited after 16μg/mL Mastoparan X treatment.
Our study demonstrated that Mastoparan X has potent bactericidal activity against MRSA and is expected to provide new potential peptides for the clinical treatment of MRSA.
耐甲氧西林金黄色葡萄球菌（MRSA）因其多重耐药性和强大的生物膜形成能力，对公共卫生系统构成严重威胁。在此，我们探讨了抗菌肽马蜂毒素X（Mastoparan X）对MRSA的可能抑制机制。
采用微量肉汤稀释法测定马蜂毒素X对MRSA USA300的最低抑菌浓度（MIC）和最低杀菌浓度（MBC）。然后通过时间-生长曲线、膜流动性、活性氧（ROS）、流式细胞术、扫描电子显微镜（SEM）和共聚焦激光扫描显微镜（CLSM）评估马蜂毒素X对USA300的抗菌活性。此外，使用结晶紫染色评估马蜂毒素X对USA300生物膜的抑制和清除作用。最后，通过转录组学分析马蜂毒素X处理后USA300的基因表达变化，并通过RT-qPCR进行验证。
马蜂毒素X对USA300的MIC和MBC分别为32μg/mL和64μg/mL。SEM观察显示马蜂毒素X处理后细胞形态有显著变化。流式细胞术证实马蜂毒素X促进了MRSA细胞的凋亡。此外，马蜂毒素X抑制了MRSA生物膜的形成，同时破坏了已形成的成熟生物被膜。转录组分析表明，16μg/mL马蜂毒素X处理后，851个基因发生显著改变，ABC转运蛋白、氨基酸生物合成、糖酵解和三羧酸（TCA）循环受到抑制。
我们的研究表明，马蜂毒素X对MRSA具有强大的杀菌活性，有望为MRSA的临床治疗提供新的潜在肽类。
