A range of opportunistic human pathogens can cause severe invasive infections. Organisms such as streptococci pyogenes and Acinetobacter baumannii have been effectively treated with antibiotics, but cases of antibiotic resistance are rising. A novel therapeutic strategy to combat human pathogens is the delivery of antisense peptide nucleic acids (PNAs) into bacteria that provide the antisense targeting of essential genes. PNA coupled to a cell-penetrating peptide (CPP) can effectively deliver the cargo into the cell. The CPP  (RXR)₄XB peptide (R, arginine; X, 6-aminohexanoic acid; B, β-alanine) conjugated to various cargo is highly effective at translocating PNA across the cell membrane. The efficiency of CPP-mediated PNA uptake is bacterial species-specific. For S. pyogenes, gyrA PNA coupled to (RXR)₄XB abolished bacterial growth.  For A. baumannii, the PNA cargo (BNA^NC-DNA) coupled to (RXR)₄XB effectively inhibited translation and bacterial growth. This suggests that the CPP  (RXR)₄XB may be an effective tool in the future for combatting the rise in strains of antibiotic-resistant bacteria.