Introduction: The LL-37 peptide, the only cathelicidin secreted in human organisms, can resist numerous pathogens as a part of an immune system. The efficiency of LL-37 antimicrobial action is dependent on the bacterial membrane composition, the percentage of phospholipid classes, their mutual proportions, and the types of fatty acid chains. The presence of choline in the growth environment for bacteria alternates the composition and physicochemical properties of their membranes, which then affects the LL-37 activity. In this study, the influence of the antimicrobial LL-37 peptide on the phospholipid monolayers at the liquid—air interface mimicking the membranes of Legionella gormanii bacteria was analyzed.
Methods: The Langmuir monolayer technique was used to prepare model membranes composed of individual classes of phospholipids (phosphatidylcholine (PC), phosphatidylethanolamine (PE), cardiolipin (CL), phosphatidylglycerol (PG), and their mixtures isolated) from L. gormanii bacteria supplemented or not with exogenous choline. In order to determine the peptide’s mechanism of action, penetration tests were carried out for the phospholipid monolayers compressed to a surface pressure of 30 mN/m, and the peptide was then dispensed to the subphase. The changes in mean molecular area were observed over time.
Results: The results show the diversified effect of LL-37 on the phospholipid monolayers depending on the bacteria growth conditions. The choline presence in the medium affects the molecular profile of phospholipids in the bacterial membranes, determining the greater activity of the peptide. Our findings demonstrate that notable peptide insertion and disruption of the lateral packing and ordering can cause membrane destabilization.
Conclusions: Changes in membrane structure due to its interactions with LL-37 demonstrate a feasible mechanism of peptide action at a molecular level. Its determination is crucial for the design and development of antimicrobial peptides as an alternative to conventional antibiotics.
