Department of Genetics, Faculty of Biology, Sofia University "St. Kliment Ohridski", 8 Dragan Tzankov Boulevard, 1164 Sofia, Bulgaria.
ACS Synth Biol. 2021 Nov 19;10(11):3167-3176. doi: 10.1021/acssynbio.1c00443. Epub 2021 Nov 4.
Due to the steady rise of multidrug-resistant pathogenic bacteria worldwide, it is critical to develop novel antibacterial drugs. This article presents chimeric antisense oligonucleotides that inhibit the bacterial growth of , one of the most frequent causes of hospital-acquired infections. The chimeric antisense oligonucleotides have a combination of first- and second-generation chemical modification. To deliver the antisense oligonucleotides into a cell, we apply a cell-penetrating oligopeptide attached to them. We have performed complete bioinformatics analyses of the glmS ribozyme present in and its essential role in the biochemical pathway of glucosamine-6-phosphate synthesis. Besides, we have analyzed the bacteria for alternative metabolic pathways, such as the gene. The first antisense oligonucleotide explicitly targets the glmS riboswitch, while the second explicitly targets the mRNA. We have evaluated that combined, the antisense oligonucleotides block the synthesis of glucosamine-6-phosphate entirely and inhibit the bacterial growth of . However, the glmS riboswitch targeting the antisense oligonucleotide is sufficient to inhibit the growth of with a MIC80 of 5 μg/mL. The glmS ribozyme is a very suitable target for antibacterial drug development with antisense oligonucleotides.
由于全球多药耐药病原菌的稳步上升，开发新型抗菌药物至关重要。本文介绍了嵌合反义寡核苷酸，它可以抑制 ，这是医院获得性感染的最常见原因之一。嵌合反义寡核苷酸具有第一代和第二代化学修饰的组合。为了将反义寡核苷酸递送到细胞中，我们应用了连接到它们上的穿透细胞的寡肽。我们已经对 glmS 核酶进行了完整的生物信息学分析，该核酶存在于 中，在葡萄糖胺-6-磷酸合成的生化途径中起着至关重要的作用。此外，我们还分析了细菌的替代代谢途径，如 基因。第一个反义寡核苷酸明确靶向 glmS 核糖开关，而第二个明确靶向 mRNA。我们已经评估了，联合使用时，反义寡核苷酸完全阻断了葡萄糖胺-6-磷酸的合成，并抑制了 的细菌生长。然而，靶向反义寡核苷酸的 glmS 核糖开关足以抑制 的生长，MIC80 为 5 μg/mL。glmS 核酶是一种非常适合用反义寡核苷酸开发抗菌药物的靶标。
