Daniel Ben Hur

Conference 2023 Live Talk

Talk title

Antimicrobial peptides against multidrug-resistant pseudomonas aeruginosa biofilm from cystic fibrosis patients

Authors and Affiliations

Daniel Ben Hur1, Gal Kapach1, Naiem Ahmad Wani1, Edo Kiper1, Moshe Ashkenazi2,5, Gill Smollan3, Natan Keller3,4, Ori Efrati2,5, Yechiel Shai1

1. Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel
2. Pediatric Pulmonology and National CF Center, Edmond and Lilly Safra Children’s Hospital, Sheba Medical Center, Ramat Gan, Israel
3. Microbiology Laboratories, Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel
4. The Department of Health Management, Ariel University, Ariel, Israel
5. Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel

Abstract

Background

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 for their properties to fight against multi-drug resistance P.aeruginosa biofilm isolated from CF patients.

Methods

A vast of biochemical biophysical and clinical methods, including a collection of sputum from CF patients, isolation and Identification of antibiotic resistance P. aeruginosa from CF sputum, antibacterial Activity (MIC) with a combination of biofilm inhibition and degradation in laboratory medium and CF sputum environment, peptide stability in CF patient sputum, confocal microscopy and evolution experiment were used.

Results

The D,L-K6L9 peptides showed antimicrobial and antibiofilm activities against multi-drug resistance P. aeruginosa from CF patients and were found to be stable and resistant to degradation by CF sputum proteases. Moreover, the peptides maintain their activity in a CF sputum environment and do not induce bacterial resistance.

Conclusions

The D,L-K6L9 are easy to produce with a high product yield, highlighting them as a promising candidate for CF treatment. Overall, these findings should assist in developing alternative treatments against resistant bacterial biofilms.