An sRNA Screen for Reversal of Quinolone Resistance in Escherichia coli

Abstract

In light of the rising prevalence of antimicrobial resistance (AMR) and the slow pace of new antimicrobial development, there has been increasing interest in the development of adjuvants that improve or restore the effectiveness of existing drugs. Here, we use a novel small RNA (sRNA) screening approach to identify genes whose knockdown increases ciprofloxacin (CIP) sensitivity in a resistant strain of Escherichia coli. 5000 sRNA constructs were initially screened on a gyrA S83L background, ultimately leading to 30 validated genes whose disruption reduces CIP resistance. This set includes genes involved in DNA replication, repair, recombination, efflux, and other regulatory systems. Our findings increase understanding of the functional interactions of DNA Gyrase, and may aid in the development of new therapeutic approaches for combating AMR.

Keywords

• antimicrobial resistance
• escherichia coli
• fluoroquinolone
• bacterial small rna
• drug targets
• adjuvant