Department of Pulmonology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, P.R. China.
Department of Respiratory Medicine, The First Hospital of Shijiazhuang, Shijiazhuang, Hebei 050011, P.R. China.
Mol Med Rep. 2019 Apr;19(4):3337-3344. doi: 10.3892/mmr.2019.9988. Epub 2019 Feb 26.
Methicillin‑resistant Staphylococcus aureus (S. aureus; MRSA) is one of the most common bacterial pathogens and MRSA infections are characterized by high mortality rates. Antimicrobial peptides are considered one of the most promising drugs for the treatment of resistant strains of S. aureus. The present study aimed to examine the antimicrobial activity of L12 against numerous bacterial species using the broth microdilution method. Furthermore, the synergistic effect of L12 combined with various antibacterial drugs was tested, and its antibacterial mechanism was investigated by a checkerboard assay. The alterations in bacterial morphology were detected by electron microscopy, and biofilm formation and removal were tested by crystal violet staining. The present results suggested that L12 affected the growth of gram‑positive strains, particularly S. aureus. Electron microscopy analysis suggested that L12 may target the cell membrane, and L12 increased the antibacterial activity of vancomycin and levofloxacin, exerting a synergistic effect. However, the minimal inhibitory concentrations (MICs) of L12 were not correlated with antibiotic resistance, the strains resistant to more antibiotics were not more resistant to L12. A sub‑MIC of L12 was able to inhibit biofilm formation in a dose‑dependent manner; however, concentrations of L12 ≤10 times the MIC were not sufficient to degrade previously formed biofilm. Collectively, the present study suggested that L12 may represent a novel potential therapeutic molecule for the treatment of S. aureus infections.
耐甲氧西林金黄色葡萄球菌(S. aureus;MRSA)是最常见的细菌病原体之一,MRSA 感染的死亡率很高。抗菌肽被认为是治疗耐甲氧西林金黄色葡萄球菌的最有前途的药物之一。本研究旨在使用肉汤微量稀释法检查 L12 对多种细菌的抗菌活性。此外,还测试了 L12 与各种抗菌药物联合使用的协同作用,并通过棋盘试验研究了其抗菌机制。通过电子显微镜检测细菌形态的变化,通过结晶紫染色检测生物膜的形成和去除。本研究结果表明,L12 影响革兰氏阳性菌株的生长,特别是金黄色葡萄球菌。电子显微镜分析表明,L12 可能靶向细胞膜,并且 L12 增加了万古霉素和左氧氟沙星的抗菌活性,发挥协同作用。然而,L12 的最小抑菌浓度(MIC)与抗生素耐药性无关,对更多抗生素耐药的菌株对 L12 的耐药性并不更高。亚 MIC 的 L12 能够以剂量依赖性方式抑制生物膜的形成;然而,浓度为 L12 ≤10 倍 MIC 不足以降解先前形成的生物膜。总之,本研究表明 L12 可能代表一种治疗金黄色葡萄球菌感染的新型潜在治疗分子。