title: Bactericidal activities of cathelicidin LL-37 and select cationic lipids against the hypervirulent Pseudomonas aeruginosa strain LESB58.
abstract: Pseudomonas aeruginosa Liverpool epidemic strain (LES) infections in cystic fibrosis (CF) patients are associated with transmissibility and increased patient morbidity. This study was designed to assess the in vitro activities of cathelicidin LL-37 peptide (LL-37) and select cationic lipids against Pseudomonas aeruginosa LESB58 in CF sputum and in a setting mimicking the CF airway. We found that LL-37 naturally present in airway surface fluid and some nonpeptide cationic lipid molecules such as CSA-13, CSA-90, CSA-131, and D2S have significant, but broadly differing, bactericidal activities against P. aeruginosa LESB58. We observed strong inhibition of LL-37 bactericidal activity in the presence of purified bacteriophage Pf1, which is highly expressed by P. aeruginosa LES, but the activities of the cationic lipids CSA-13 and CSA-131 were not affected by this polyanionic virus. Additionally, CSA-13 and CSA-131 effectively prevent LESB58 biofilm formation, which is stimulated by Pf1 bacteriophage, DNA, or F-actin. CSA-13 and CSA-131 display strong antibacterial activities against different clinical strains of P. aeruginosa, and their activities against P. aeruginosa LESB58 and Xen5 strains were maintained in CF sputum. These data indicate that synthetic cationic lipids (mimics of natural antimicrobial peptides) are suitable for developing an effective treatment against CF lung P. aeruginosa infections, including those caused by LES strains.
authors: Department of Microbiological and Nanobiomedical Engineering, Medical University of Białystok, Białystok, Poland.
authors: Urszula
authors: U
authors: Wnorowska
authors: Department of Microbiological and Nanobiomedical Engineering, Medical University of Białystok, Białystok, Poland.
authors: Katarzyna
authors: K
authors: Niemirowicz
authors: Department of Chemical and Biomolecular Engineering, Institute for Medicine and Engineering, Penn Center for Molecular Discovery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors: Melissa
authors: M
authors: Myint
authors: Department of Chemical and Biomolecular Engineering, Institute for Medicine and Engineering, Penn Center for Molecular Discovery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors: Scott L
authors: SL
authors: Diamond
authors: Department of Dental Microbiology, Medical University of Warsaw, Warsaw, Poland.
authors: Marta
authors: M
authors: Wróblewska
authors: Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah, USA.
authors: Paul B
authors: PB
authors: Savage
authors: Department of Physiology and Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors: Paul A
authors: PA
authors: Janmey
authors: Department of Microbiological and Nanobiomedical Engineering, Medical University of Białystok, Białystok, Poland Department of Physiology and Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA Department of Physiology, Pathophysiology and Microbiology of Infections, The Faculty of Health Sciences, Jan Kochanowski University, Kielce, Poland buckirobert@gmail.com.
authors: Robert
authors: R
authors: Bucki
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D025561:Bacteriophage Pf1 / Q000472:pathogenicity; D018441:Biofilms / Q000187:drug effects; D003550:Cystic Fibrosis / Q000382:microbiology; D006801:Humans; D008055:Lipids / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D018625:Microscopy, Atomic Force; D008954:Models, Biological; D011278:Pregnanes / Q000494:pharmacology; D011437:Propylamines / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000472:pathogenicity; D013256:Steroids / Q000494:pharmacology*; D054804:Cathelicidins
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; C000597011:CSA-90; D008055:Lipids; D011278:Pregnanes; D011437:Propylamines; D013256:Steroids; C521528:ceragenin CSA-13; D054804:Cathelicidins