Disruption of sRNA Function Using Synthetic Arginine Rich Motif Peptides

Abstract

Small RNAs (sRNAs) regulate the expression of many genes including those involved in antibiotic resistance and bacterial virulence, making them potential therapeutic targets. A molecule that binds an sRNA could interfere with its ability to bind its target mRNA and disrupt the regulation mechanism. Randomization and screening of natural arginine rich motif (ARM) peptides led to peptides capable of interfering with the sRNA MicF's ability to regulate ompF in Escherichia coli. Molecular dynamics simulations suggested that this effect was not a result of a direct disruption of the MicF-ompF interaction. Instead, the peptides interfere with binding of the chaperone Hfq, which is required for MicF-mediated regulation. Subsequent testing demonstrated peptide specificity for MicF over two other Hfq scaffolds and the ability to disrupt regulation of two additional MicF targets. Together, these findings support the use of synthetic ARMs as a potential tool for modulating sRNA function in bacteria.