Can Vitamin B12 Assist the Internalization of Antisense LNA Oligonucleotides into Bacteria?
| Autor: | Ruwei Yao, Rita S. Santos, Nuno F. Azevedo, Per T. Jørgensen, M. J. M. Gomes, Sara Pereira, Jesper Wengel |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Microbiology (medical) media_common.quotation_subject 030106 microbiology antibacterial drug medicine.disease_cause nucleic acid mimics 2′OMe Biochemistry Microbiology Article 03 medical and health sciences In vivo Antibacterial drug medicine Pharmacology (medical) General Pharmacology Toxicology and Pharmaceutics Internalization Escherichia coli media_common Nucleic acid mimics Antisense oligonucleotides Vitamin B12 biology vitamin B12 Oligonucleotide Chemistry 20OMe lcsh:RM1-950 biology.organism_classification lcsh:Therapeutics. Pharmacology 030104 developmental biology Infectious Diseases LNA Nucleic acid Cell envelope antisense oligonucleotides Bacterial outer membrane Bacteria |
| Zdroj: | Antibiotics Antibiotics, Vol 10, Iss 379, p 379 (2021) Pereira, S, Yao, R, Gomes, M, Jørgensen, P T, Wengel, J, Azevedo, N F & Santos, R S 2021, ' Can Vitamin B12 Assist the Internalization of Antisense LNA Oligonucleotides into Bacteria? ', Antibiotics, vol. 10, no. 4, 379 . https://doi.org/10.3390/antibiotics10040379 Volume 10 Issue 4 |
| ISSN: | 2079-6382 |
| DOI: | 10.3390/antibiotics10040379 |
| Popis: | The emergence of bacterial resistance to traditional small-molecule antibiotics is fueling the search for innovative strategies to treat infections. Inhibiting the expression of essential bacterial genes using antisense oligonucleotides (ASOs), particularly composed of nucleic acid mimics (NAMs), has emerged as a promising strategy. However, their efficiency depends on their association with vectors that can translocate the bacterial envelope. Vitamin B12 is among the largest molecules known to be taken up by bacteria and has very recently started to gain interest as a trojan-horse vector. Gapmers and steric blockers were evaluated as ASOs against Escherichia coli (E. coli). Both ASOs were successfully conjugated to B12 by copper-free azide-alkyne click-chemistry. The biological effect of the two conjugates was evaluated together with their intracellular localization in E. coli. Although not only B12 but also both B12-ASO conjugates interacted strongly with E. coli, they were mostly colocalized with the outer membrane. Only 6–9% were detected in the cytosol, which showed to be insufficient for bacterial growth inhibition. These results suggest that the internalization of B12-ASO conjugates is strongly affected by the low uptake rate of the B12 in E. coli and that further studies are needed before considering this strategy against biofilms in vivo. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|