2. Academic Validation
  3. Insight into the Mechanism of Interactions between the LL-37 Peptide and Model Membranes of Legionella gormanii Bacteria

Insight into the Mechanism of Interactions between the LL-37 Peptide and Model Membranes of Legionella gormanii Bacteria

  • Int J Mol Sci. 2023 Jul 27;24(15):12039. doi: 10.3390/ijms241512039.
Katarzyna Pastuszak 1,  Bozena Kowalczyk 2,  Jacek Tarasiuk 2,  Rafal Luchowski 3,  Wieslaw I Gruszecki 3,  Małgorzata Jurak 1,  Marta Palusinska-Szysz 2
Affiliations

Affiliations

  • 1 Department of Interfacial Phenomena, Institute of Chemical Sciences, Faculty of Chemistry, Maria Curie-Skłodowska University, Maria Curie-Skłodowska Sq. 3, 20-031 Lublin, Poland.
  • 2 Department of Genetics and Microbiology, Institute of Biological Sciences, Faculty of Biology and Biotechnology, Maria Curie-Skłodowska University, Akademicka 19, 20-033 Lublin, Poland.
  • 3 Department of Biophysics, Institute of Physics, Faculty of Mathematics, Physics and Informatics, Maria Curie-Skłodowska University, Radziszewskiego 10, 20-031 Lublin, Poland.
PMID: 37569419 DOI: 10.3390/ijms241512039
Abstract

Legionella gormanii is a fastidious, Gram-negative bacterium known to be the etiological agent of atypical community-acquired pneumonia. The human cathelicidin LL-37 exhibits a dose-dependent bactericidal effect on L. gormanii. The LL-37 peptide at the concentration of 10 µM causes the bacteria to become viable but not cultured. The Antibacterial activity of the peptide is attributed to its effective binding to the Bacterial membrane, as demonstrated by the fluorescence lifetime imaging microscopy. In this study, to mimic the L. gormanii membranes and their response to the antimicrobial peptide, Langmuir monolayers were used with the addition of the LL-37 peptide to the subphase of the Langmuir trough to represent the extracellular fluid. The properties of the model membranes (Langmuir monolayers) formed by Phospholipids (PL) isolated from the L. gormanii bacteria cultured on the non-supplemented (PL-choline) and choline-supplemented (PL+choline) medium were determined, along with the effect of the LL-37 peptide on the intermolecular interactions, packing, and ordering under the monolayer compression. Penetration tests at the constant surface pressure were carried out to investigate the mechanism of the LL-37 peptide action on the model membranes. The peptide binds to the anionic Bacterial membranes preferentially, due to its positive charge. Upon binding, the LL-37 peptide can penetrate into the hydrophobic tails of Phospholipids, destabilizing membrane integrity. The above process can entail membrane disruption and ultimately cell death. The ability to evoke such a great membrane destabilization is dependent on the share of electrostatic, hydrogen bonding and Lifshitz-van der Waals LL-37-PL interactions. Thus, the LL-37 peptide action depends on the changes in the lipid membrane composition caused by the utilization of exogenous choline by the L. gormanii.

Keywords

LL-37; Langmuir monolayer technique; Legionella gormanii.

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