2. Academic Validation
  3. Antimicrobial Peptides against Multidrug-Resistant Pseudomonas aeruginosa Biofilm from Cystic Fibrosis Patients

Antimicrobial Peptides against Multidrug-Resistant Pseudomonas aeruginosa Biofilm from Cystic Fibrosis Patients

  • J Med Chem. 2022 Jul 14;65(13):9050-9062. doi: 10.1021/acs.jmedchem.2c00270.
Daniel Ben Hur 1,  Gal Kapach 1,  Naiem Ahmad Wani 1,  Edo Kiper 1,  Moshe Ashkenazi 2 3,  Gill Smollan 4,  Natan Keller 5 4,  Ori Efrati 2 3,  Yechiel Shai 1
Affiliations

Affiliations

  • 1 Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 76100, Israel.
  • 2 Pediatric Pulmonary Institute and National CF Center, Edmond and Lilly Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Ramat Gan 52621, Israel.
  • 3 Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel.
  • 4 Microbiology Laboratories, Edmond and Lili Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Ariel University, Ramat Gan 52621, Israel.
  • 5 The Department of Health Management, Ariel University, Ariel 40700, Israel.
PMID: 35759644 DOI: 10.1021/acs.jmedchem.2c00270
Abstract

Lung Infection is the leading cause of morbidity and mortality in cystic fibrosis (CF) patients and is mainly dominated by Pseudomonas aeruginosa. Treatment of CF-associated lung infections is problematic because the drugs are vulnerable to multidrug-resistant pathogens, many of which are major biofilm producers like P. aeruginosa. Antimicrobial Peptides (AMPs) are essential components in all life forms and exhibit antimicrobial activity. Here we investigated a series of AMPs (d,l-K6L9), each composed of six lysines and nine leucines but differing in their sequence composed of l- and d-amino acids. The d,l-K6L9 Peptides showed antimicrobial and antibiofilm activities against P. aeruginosa from CF patients. Furthermore, the data revealed that the d,l-K6L9 Peptides are stable and resistant to degradation by CF sputum proteases and maintain their activity in a CF sputum environment. Additionally, the d,l-K6L9 Peptides do not induce Bacterial resistance. Overall, these findings should assist in the future development of alternative treatments against resistant Bacterial biofilms.

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