[Antisense oligonucleotides inhibiting ribosomal functions in mycobacteria]

Area of Science:

• Microbiology
• Molecular Biology
• Antimicrobial Research

Background:

• Antimicrobial resistance is a growing global health threat.
• Targeting essential bacterial processes like protein synthesis is a key strategy for developing new antibiotics.
• Ribosomal RNA (rRNA) is a crucial component of bacterial ribosomes and a potential target for antimicrobial agents.

Purpose of the Study:

• To investigate the binding of antisense oligonucleotides (ASOs) to the 23S ribosomal RNA (rRNA) of mycobacteria and Escherichia coli.
• To identify ASOs with selective affinity for specific regions of mycobacterial 23S rRNA and ribosomes.
• To evaluate the efficacy of identified ASOs in inhibiting protein synthesis in mycobacteria.

Main Methods:

• Design and synthesis of antisense oligonucleotides.
• In vitro binding assays to assess ASO affinity to 23S rRNA and 70S ribosomes from M. tuberculosis and M. smegmatis.
• Protein synthesis inhibition assays using M. smegmatis ribosomes.

Main Results:

• Identified ASOs exhibiting selective binding to the alpha-sarcin loop region of 23S rRNA from Mycobacterium tuberculosis.
• Discovered ASOs with selective affinity for the 70S ribosomes of Mycobacterium smegmatis.
• Demonstrated that these selected ASOs effectively and selectively inhibit protein synthesis on M. smegmatis ribosomes.

Conclusions:

• Antisense oligonucleotides can be designed to selectively target mycobacterial rRNA and ribosomes.
• Selective inhibition of protein synthesis in M. smegmatis by specific ASOs has been achieved.
• These findings support the potential of ASOs as a novel therapeutic approach against mycobacterial infections.