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Article

Development of Novel Peptides for the Antimicrobial Combination Therapy against Carbapenem-Resistant Acinetobacter baumannii Infection

1
Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Korea
2
Division of Infectious Diseases, Department of Internal Medicine, Korea University College of Medicine, Seoul 02841, Korea
*
Author to whom correspondence should be addressed.
Academic Editor: Clive Prestidge
Pharmaceutics 2021, 13(11), 1800; https://doi.org/10.3390/pharmaceutics13111800
Received: 31 August 2021 / Revised: 20 October 2021 / Accepted: 25 October 2021 / Published: 27 October 2021
Carbapenem-resistant Acinetobacter baumannii (CRAB) infection has a high mortality rate, making the development of novel effective antibiotic therapeutic strategies highly critical. Antimicrobial peptides can outperform conventional antibiotics regarding drug resistance and broad-spectrum activity. PapMA, an 18-residue hybrid peptide, containing N-terminal residues of papiliocin and magainin 2, has previously demonstrated potent antibacterial activity. In this study, PapMA analogs were designed by substituting Ala15 or Phe18 with Ala, Phe, and Trp. PapMA-3 with Trp18 showed the highest bacterial selectivity against CRAB, alongside low cytotoxicity. Biophysical studies revealed that PapMA-3 permeabilizes CRAB membrane via strong binding to LPS. To reduce toxicity via reduced antibiotic doses, while preventing the emergence of multi-drug resistant bacteria, the efficacy of PapMA-3 in combination with six selected antibiotics was evaluated against clinical CRAB isolates (C1–C5). At 25% of the minimum inhibition concentration, PapMA-3 partially depolarized the CRAB membrane and caused sufficient morphological changes, facilitating the entry of antibiotics into the bacterial cell. Combining PapMA-3 with rifampin significantly and synergistically inhibited CRAB C4 (FICI = 0.13). Meanwhile, combining PapMA-3 with vancomycin or erythromycin, both potent against Gram-positive bacteria, demonstrated remarkable synergistic antibiofilm activity against Gram-negative CRAB. This study could aid in the development of combination therapeutic approaches against CRAB. View Full-Text
Keywords: antimicrobial peptides; antibiotics; synergistic effect; CRAB antimicrobial peptides; antibiotics; synergistic effect; CRAB
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MDPI and ACS Style

Choi, J.; Jang, A.; Yoon, Y.K.; Kim, Y. Development of Novel Peptides for the Antimicrobial Combination Therapy against Carbapenem-Resistant Acinetobacter baumannii Infection. Pharmaceutics 2021, 13, 1800. https://doi.org/10.3390/pharmaceutics13111800

AMA Style

Choi J, Jang A, Yoon YK, Kim Y. Development of Novel Peptides for the Antimicrobial Combination Therapy against Carbapenem-Resistant Acinetobacter baumannii Infection. Pharmaceutics. 2021; 13(11):1800. https://doi.org/10.3390/pharmaceutics13111800

Chicago/Turabian Style

Choi, Joonhyeok, Ahjin Jang, Young K. Yoon, and Yangmee Kim. 2021. "Development of Novel Peptides for the Antimicrobial Combination Therapy against Carbapenem-Resistant Acinetobacter baumannii Infection" Pharmaceutics 13, no. 11: 1800. https://doi.org/10.3390/pharmaceutics13111800

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