Cecropin-B peptide

Pseudomonas aeruginosa is an opportunisticbacterial pathogen causing severe infections in hospitalizedand immunosuppressed patients, particularly individuals affectedby cystic fibrosis. Several clinically isolated P. aeruginosa strainswere found to be resistant to three or more antimicrobial classesindicating the importance of identifying new antimicrobialsactive against this pathogen. Here, we characterized theantimicrobial activity and the action mechanisms against P.aeruginosa of two natural isoforms of the antimicrobial peptidececropin B, both isolated from the silkworm Bombyx mori.These cecropin B isoforms differ in a single amino acidsubstitution within the active portion of the peptide, so that theglutamic acid of the E53 CecB variant is replaced by a glutaminein the Q53 CecB isoform. Both peptides showed a high antimicrobial and membranolytic activity against P. aeruginosa, withQ53 CecB displaying greater activity compared with the E53 CecB isoform. Biophysical analyses, live-cell NMR, and moleculardynamic-simulation studies indicated that both peptides might act as membrane-interacting elements, which can disrupt outermembraneorganization, facilitating their translocation toward the inner membrane of the bacterial cell. Our data also suggestthat the amino acid variation of the Q53 CecB isoform represents a critical factor in stabilizing the hydrophobic segment thatinteracts with the bacterial membrane, determining the highest antimicrobial activity of the whole peptide. Its high stability topH and temperature variations, tolerance to high salt concentrations, and low toxicity against human cells make Q53 CecB apromising candidate in the development of CecB-derived compounds against P. aeruginosa.