Identification of potential therapeutic antimicrobial peptides against Acinetobacter baumannii in a mouse model of pneumonia

  • Sci Rep. 2021 Apr 1;11(1):7318. doi: 10.1038/s41598-021-86844-5.
Chiau-Jing Jung  1 ,  You-Di Liao  2 ,  Chih-Chieh Hsu  3 ,  Ting-Yu Huang  4 ,  Yu-Chung Chuang  5 ,  Jeng-Wei Chen  6  7 ,  Yu-Min Kuo  7 ,  Jean-San Chia  8  9
Affiliations
  • 1. Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, No. 250, Wuxing Street, Taipei, 11031, Taiwan. [email protected].
  • 2. Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
  • 3. Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan.
  • 4. Graduate Institute of Microbiology, College of Medicine, National Taiwan University, No. 1, Jen Ai Road Section 1, Taipei, 10051, Taiwan.
  • 5. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
  • 6. Division of Cardiovascular Surgery, Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
  • 7. Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
  • 8. Graduate Institute of Microbiology, College of Medicine, National Taiwan University, No. 1, Jen Ai Road Section 1, Taipei, 10051, Taiwan. [email protected].
  • 9. Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan. [email protected].
PMID: 33795739 DOI: 10.1038/s41598-021-86844-5
Abstract

Acinetobacter baumannii-induced nosocomial pneumonia has become a serious clinical problem because of high Antibiotic resistance rates. Antimicrobial peptides (AMP) are an ideal alternative strategy due to their broad-spectrum of antimicrobial activity and low incidence of Bacterial resistance. However, their application is limited by toxicity and stability in vivo. The present study used a mouse model to directly identify potential AMPs effective for treatment of A. baumannii-induced pneumonia. Fifty-eight AMPs were screened and two identified (SMAP-29 and TP4) to have prophylactic effects which prevented the death of mice with pneumonia. Furthermore, two TP4 derivatives (dN4 and dC4) were found to have therapeutic activity in pneumonia mouse models by peritoneal or intravenous administration. Both dN4 and dC4 also inhibited and/or eliminated A. baumannii biofilms at higher doses. Taken together, these data suggest the AMP derivatives dN4 and dC4 represent a potential treatment strategy for A. baumannii-induced pneumonia.

Products