Transcriptome-based design of antisense inhibitors potentiates carbapenem efficacy in CRE Escherichia coli

Significance Carbapenem resistance has become steadily more common in recent decades, and its prevalence in Enterobacteriaceae has been marked as an urgent antibiotic priority by both the World Health Organization and the US Centers for Disease Control and Prevention. In this paper, we use RNA sequencing to explore resistance development and engineer peptide nucleic acids (PNA) for bacterial growth inhibition. Our results mark the use of transcriptomics for the design of antibiotic PNA and demonstrate that this method of PNA design can be equally or more effective than standard genome-based design. Furthermore, we identify three genes that may point to antibiotic targets and two genes that offer clues about how Enterobacteriaceae acquire carbapenem resistance.