Combinatorial PNA-CPP Molecules Targeting Plasmid Transfer and Replication to Control Antibiotic Resistance

One major cause of the widespread of drug-resistant and virulent bacteria pathogen is the horizontal gene transfer of resistance and virulence genes in the form of plasmids. As proof-of concept for this Phase I effort, Agave BioSystems proposes to develop combinatorial therapeutics by inhibiting conserved genes involved in multiple steps of plasmid transfer and replication using peptide nucleic acid (PNA) antisense oligonucleotides and cell penetrating peptides (CPPs) in both gram-negative bacteria Escherichia coli and gram-positive strain Enterococcus faecalis. These PNA-CPPs are designed to suppress the expression of the critical enzymes involved in the plasmid transfer and replication in the pathogenic microorganisms. The proposed system has the potential to inhibit the spread of drug resistance genes to susceptible strains and eventually eliminate the drug resistance of the host microbes.