A synthetic peptide sensitizes multi-drug resistant Pseudomonas aeruginosa to antibiotics for more than two hours and permeabilizes its envelope for twenty hours.

Background: Pseudomonas aeruginosa is a Gram-negative pathogen that frequently causes life-threatening infections in immunocompromised patients. We previously showed that subinhibitory concentrations of short synthetic peptides permeabilize P. aeruginosa and enhance the lethal action of co-administered antibiotics.

Bacterial cell wall compounds as promising targets of antimicrobial agents I. Antimicrobial peptides and lipopolyamines.

The first barrier that an antimicrobial agent must overcome when interacting with its target is the microbial cell wall. In the case of Gram-negative bacteria, additional to the cytoplasmic membrane and the peptidoglycan layer, an outer membrane (OM) is the outermost barrier. The OM has an asymmetric distribution of the lipids with phospholipids and lipopolysaccharide (LPS) located in the inner and outer leaflets, respectively.

Biophysical mechanisms of endotoxin neutralization by cationic amphiphilic peptides.

Bacterial endotoxins (lipopolysaccharides (LPS)) are strong elicitors of the human immune system by interacting with serum and membrane proteins such as lipopolysaccharide-binding protein (LBP) and CD14 with high specificity. At LPS concentrations as low as 0.3 ng/ml, such interactions may lead to severe pathophysiological effects, including sepsis and septic shock.

Physicochemical and biological characterization of anti-endotoxin peptides and their influence on lipid properties.

We have synthesized a series of short peptides (17 to 20 amino acids), originally derived from Limulus anti-lipopolysaccharide factor LALF, which were primarily designed to act as antimicrobial agents as well as neutralizers of bacterial endotoxin (lipopolysaccharide, LPS), Here, two selected peptides, a 17- and a 19-mer, were characterized physicochemically and in biological test systems. The secondary structure of the peptides indicates essentially a β-sheet including antiparallel strands, the latter being reduced when the peptides bind to LPS. A very strong exothermic binding due to attractive Coulomb interactions governs the LPS-peptide reaction, which additionally leads to a fluidization of the acyl chains of LPS.

New antiseptic peptides to protect against endotoxin-mediated shock.

Systemic bacterial infections are associated with high mortality. The access of bacteria or constituents thereof to systemic circulation induces the massive release of immunomodulatory mediators, ultimately causing tissue hypoperfusion and multiple-organ failure despite adequate antibiotic treatment. Lipid A, the "endotoxic principle" of bacterial lipopolysaccharide (LPS), is one of the major bacterial immunostimuli.