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

Autor: Ben Hur D; Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 76100, Israel., Kapach G; Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 76100, Israel., Wani NA; Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 76100, Israel., Kiper E; Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 76100, Israel., Ashkenazi M; Pediatric Pulmonary Institute and National CF Center, Edmond and Lilly Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Ramat Gan 52621, Israel.; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel., Smollan G; Microbiology Laboratories, Edmond and Lili Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Ariel University, Ramat Gan 52621, Israel., Keller N; The Department of Health Management, Ariel University, Ariel 40700, Israel.; Microbiology Laboratories, Edmond and Lili Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Ariel University, Ramat Gan 52621, Israel., Efrati O; Pediatric Pulmonary Institute and National CF Center, Edmond and Lilly Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Ramat Gan 52621, Israel.; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel., Shai Y; Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 76100, Israel.
Jazyk: angličtina
Zdroj: Journal of medicinal chemistry [J Med Chem] 2022 Jul 14; Vol. 65 (13), pp. 9050-9062. Date of Electronic Publication: 2022 Jun 27.
DOI: 10.1021/acs.jmedchem.2c00270
Abstrakt: 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-K 6 L 9 ), each composed of six lysines and nine leucines but differing in their sequence composed of l- and d-amino acids. The d,l-K 6 L 9 peptides showed antimicrobial and antibiofilm activities against P. aeruginosa from CF patients. Furthermore, the data revealed that the d,l-K 6 L 9 peptides are stable and resistant to degradation by CF sputum proteases and maintain their activity in a CF sputum environment. Additionally, the d,l-K 6 L 9 peptides do not induce bacterial resistance. Overall, these findings should assist in the future development of alternative treatments against resistant bacterial biofilms.
Databáze: MEDLINE