使用转录因子诱作为vanA运抑制剂,恢复对抗耐药Enterococcus faecalis的万科胺活性
Loai M Abdelall1, Yosra Ibrahim Nagy2, Mona T Kashef2
1Department of General Administration of Factories Inspection, Central Administration of Operations, Egyptian Drug Authority, Giza 12654, Egypt.
The Journal of antimicrobial chemotherapy
|September 10, 2024
概括
一种新型的转录因子诱 (TFD) 系统有效地抑制了万科米辛耐药性肠球菌 (VRE) 中的vanA基因. 这种TFD-lipoplex疗法恢复了万科米辛的敏感性,并在体内根除了VRE感染.
科学领域:
- 微生物学 微生物学
- 基因治疗 基因治疗
- 抗微生物耐药性 抗微生物耐药性
背景情况:
- 由于治疗选择有限,抗万科素的肠球菌 (VRE) 构成了严重的公共卫生威胁.
- 范A操作子是肠球菌中获得的万通素耐药性的主要遗传决定因素.
- 开发新的策略来打击VRE至关重要.
研究的目的:
- 开发一种针对vanA基因的转录因子诱 (TFD) 系统.
- 抑制vanA基因转录作为对抗VRE的治疗策略.
- 评估TFD-lipoplex在恢复万科米辛活性方面的疗效和安全性.
主要方法:
- 在存在TFD-lipoplexes时确定万科米辛最小抑制度 (MIC).
- 评估了TFD-lipoplexes对vanA基因表达和E. faecalis生长的影响.
- 评估了TFD-lipoplexes的血液溶解活性和细胞毒性.
- 在体内测试的疗效使用系统性小鼠感染模型与抗万科素的E. faecalis (VREF).
主要成果:
- TFD-lipoplex 减少了对VRE的万科米辛MIC,从256 mg/L降至16 mg/L.
- TFD-lipoplexes降低了vanA基因转录的约3倍,而不会影响E. faecalis的生长.
- TFD-lipoplex没有表现出明显的血液溶解或细胞毒性作用.
- 同时使用TFD-lipoplex和万科米有效地在体内根除了VREF感染.
结论:
- 开发的TFD-lipoplex成功地恢复了针对VREF的万科素活性.
- 这种方法为VRE感染提供了安全有效的非传统疗法.
- 呈现了基因治疗中的潜在革命,适用于其他耐药基因.
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