Bactericidal Activities of Cathelicidin LL-37 and Select Cationic Lipids against the Hypervirulent Pseudomonas aeruginosa Strain LESB58

Author:

Wnorowska Urszula,Niemirowicz Katarzyna,Myint Melissa,Diamond Scott L.,Wróblewska Marta,Savage Paul B.,Janmey Paul A.,Bucki Robert

Abstract

ABSTRACTPseudomonas aeruginosaLiverpool epidemic strain (LES) infections in cystic fibrosis (CF) patients are associated with transmissibility and increased patient morbidity. This study was designed to assess thein vitroactivities of cathelicidin LL-37 peptide (LL-37) and select cationic lipids againstPseudomonas aeruginosaLESB58 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 againstP. aeruginosaLESB58. We observed strong inhibition of LL-37 bactericidal activity in the presence of purified bacteriophage Pf1, which is highly expressed byP. aeruginosaLES, 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 ofP. aeruginosa, and their activities againstP. aeruginosaLESB58 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 lungP. aeruginosainfections, including those caused by LES strains.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

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