Identifying Antisense Oligonucleotides to Disrupt Small RNA Regulated Antibiotic Resistance via a Cell-Free Transcription-Translation Platform.

ABSTRACT: Bacterial small RNAs (sRNAs) regulate many important physiological processes in cells, including antibiotic resistance and virulence genes, through base-pairing interactions with mRNAs. Antisense oligonucleotides (ASOs) have great potential as therapeutics against bacterial pathogens by targeting sRNAs such as MicF, which regulates outer membrane protein OmpF expression and limits the permeability of antibiotics. Here we devised a cell-free transcription-translation (TX-TL) assay to identify ASO designs that sufficiently sequester MicF. ASOs were then ordered as peptide nucleic acids conjugated to cell-penetrating peptides (CPP-PNA) to allow for effective delivery into bacteria. Subsequent minimum inhibitory concentration (MIC) assays demonstrated that simultaneously targeting the regions

SUBMITTER: Tsai MJ 

PROVIDER: S-EPMC10443041 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature