The Anti-Pseudomonal Peptide D-BMAP18 Is Active in Cystic Fibrosis Sputum and Displays Anti-Inflammatory In Vitro Activity.

Most Cystic Fibrosis (CF) patients succumb to airway inflammation and pulmonary infections due toPseudomonas aeruginosa.D-BMAP18, a membrane-permeabilizing antimicrobial peptide composed of D-amino acids, was evaluated as a possible antibacterial aimed to address this issue. The antipseudomonal activity ofD-BMAP18 was tested in a pathophysiological context. The peptide displayed activity against CF isolates ofPseudomonas aeruginosain the presence of CF sputum when combined with sodium chloride and DNase I. In combination with DNase I,D-BMAP18 discouraged the deposition of new biofilm and eradicated preformed biofilms of someP. aeruginosastrains. In addition,D-BMAP18 down regulated the production of TNF-alpha, IL1-beta, and TGF-beta in LPS-stimulated or IFN-gamma macrophages derived from THP-1 cells indicating an anti-inflammatory activity. The biocompatibility ofD-BMAP18 was assessed using four different cell lines, showing that residual cell-specific cytotoxicity at bactericidal concentrations could be abolished by the presence of CF sputum. Overall, this study suggests thatD-BMAP18 may be an interesting molecule as a starting point to develop a novel therapeutic agent to simultaneously contrast lung infections and inflammation in CF patients.