1. Academic Validation
  2. 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.
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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