Efficient Delivery of Antisense Oligonucleotides by Amphipathic Cell-penetrating Peptide in Acinetobacter baumannii
Efficient Delivery of Antisense Oligonucleotides by Amphipathic Cell-penetrating Peptide in Acinetobacter baumannii
复制标题
鲍曼不动杆菌中两亲性细胞穿透肽有效递送反义寡核苷酸
DOI：
10.2174/1567201816666190627141931
复制
发表时间：
2019-01-01
影响因子：
2.4
通讯作者：
Xue, Xiaoyan
中科院分区：
文献类型：
--
作者：
Chen, Zhou;Nie, Dan;Xue, Xiaoyan
背景：耐碳青霉烯类鲍曼不动杆菌(A.baumannii)在2017年世界卫生组织公布的最具威胁细菌名单中位居榜首。反义寡核苷酸(ASOS)治疗多药耐药(MDR)细菌具有特异性高、设计简单、耐药诱导率低等优点，但细菌对细胞的摄取不足限制了该疗法的进一步应用。方法：利用Cady，一种能成功携带siRNA进入哺乳动物细胞的二级两亲性多肽，制备针对acpP(编码酰基载体蛋白)的Cady/AsOS纳米粒子(Cady-NPs)，评价其摄取特性、ClDY-NPs对基因表达的抑制作用以及对MDR-A细胞生长的抑制作用。结果：我们发现Cady-NPs能被药物敏感和MDR-A迅速内化。该作用不依赖于能量，可被氯丙嗪显著抑制。另外，靶向acpP的Cady-NPs对MDR-A的生长有抑制作用。结论：本研究首次证实了CADY能将ASOS导入细菌，为MDR-A的治疗提供了一种新的策略。鲍曼尼。
Background: Carbapenem resistant Acinetobacter baumannii (A. baumannii) was on the top of the list of the most threatening bacteria published by the WHO in 2017. Antisense oligonucleotides (ASOs) based therapy is a promising strategy for combating Multi-Drug Resistant (MDR) bacteria because of its high specificity, easy design and lower induction of resistance, but poor cellular uptake by bacteria has restricted the further utilization of this therapy.Methods: Here, we used CADY, a secondary amphipathic peptide of 20 residues that could successfully carry siRNA into mammalian cells, to prepare CADY/ASOs nanoparticles (CADY-NPs) targeting acpP (encoding acyl carrier protein), and evaluated the uptake features, the inhibitory effects of ClDY-NPs on gene expression and the growth of MDR-A. baumannii.Results: We found that CADY-NPs could be quickly internalized by drug-sensitive and MDR-A. baumannii in an energy independent manner, which could be restrained by chlorpromazine (an inhibitor of clathrin mediated endocytosis) significantly. In addition, CADY-NPs targeting acpP concentrationdependently retarded the growth of MDR-A. baumannii, which was associated with the decreased expression of targeted genes in A. baumannii.Conclusion: In conclusion, our research is the first to demonstrate that CADY can deliver ASOs into bacteria and provide a novel strategy for the treatment of MDR-A. baumannii.