Targeting carA Using Optimized Antisense Peptide Nucleic Acid–Cell-Penetrating Peptide Conjugates in Acinetobacter baumannii: A Novel Antibacterial Approach
Year: 2025
Type: article
Abstract: Acinetobacter baumannii is an opportunistic pathogen associated with severe bloodstream infections. It exhibits a high level of multidrug resistance, posing major clinical challenges. Antisense peptide nucleic acids (PNAs) represent a promising alternative to conventional antibiotics; however, their therapeutic efficacy depends on optimal delivery and molecular design. In this study, we aimed to enhance the antibacterial activity of PNAs against A. baumannii by systematically optimizing cell-penetrating peptides (CPPs), PNA length, target region, and chemical modifications. The efficacy and safety of CPP–PNA constructs were evaluated using a comprehensive set of approaches, including determination of minimum bactericidal and minimum inhibitory concentrations, quantitative reverse transcription polymerase chain reaction, Western blotting, and cytotoxicity assays. Three CPP–PNA constructs targeting carA were synthesized. Among these, the KFFK (FFK)2–PNA conjugate showed the strongest bacterial growth-inhibitory effect, while the addition of extra lysine residues reduced its efficacy. Further analyses showed that a 10-mer alpha (α)-PNA modification targeting the ribosomal binding site of carA had the greatest inhibitory effect. These results underscore the importance of rational CPP design and PNA optimization in developing effective antisense antimicrobials against A. baumannii.
DOI: 10.3390/ijms26199526
Authors: Ju-Hui Seo, Yoo-Jeong Kim, Wook-Jong Jeon, Jung-Sik Yoo, Dong-Chan Moon
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,499
Award: G3456196404
OpenAlex ID: W4414652859