(129h) Bacterial Vesicles Act As Decoys Against the Antimicrobial Peptide, LL-37

Antimicrobial peptides (AMPs) are short, cationic, amphiphilic peptides that bind electrostatically to the negatively charged bacterial surface. Recently, evidence has emerged that bacterial outer membrane vesicles (OMVs), with their surface properties that resemble the surface of the parent bacterium, act as “decoys”, preventing the antibacterial activity of the peptides. The specific factors that regulate this decoy activity remain unclear, however. We compared the decoy activity of vesicles produced by several Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, and Aggregatibacter actinomycetemcomitans) against the human AMP, LL-37, and correlated this activity to the affinity of LL-37 for each type of vesicle. To isolate the role of specific membrane properties in this decoy activity, including charge and saturation, we compared our results to those obtained using liposomes with controlled lipid compositions. We observed that all of the tested vesicles were protective against LL-37 to some extent, with vesicles produced by P. aeruginosa displaying much stronger decoy activity than either E. coli or A. actinomycetemcomitans OMVs. Liposomes with increased amounts of negatively charged phosphatidylglycerol (PG) were more protective than those composed of neutrally charged lipids; however, charge alone did not fully explain the results obtained with the bacterial vesicles, as P. aeruginosa were not the most highly charged vesicles used. Rather, our results indicate that the PG composition regulates LL-37 binding, suggesting that LL-37 binds specifically to PG-containing membranes.