The human LL-37 peptide exerts antimicrobial activity against Legionella micdadei interacting with membrane phospholipids.
Palusińska-Szysz. Marta M; Jurak. Małgorzata M; Gisch. Nicolas N; Waldow. Franziska F; Zehethofer. Nicole N; Nehls. Christian C; Schwudke. Dominik D; Koper. Piotr P; Mazur. Andrzej A
Key Findings
- Legionella micdadei uses external choline to build phosphatidylcholine mainly via the Pcs pathway.
- Adding choline slightly alters the bacterial membrane, increasing certain lipids like phosphatidylcholine and phosphatidylglycerol.
- LL‑37 peptide kills L. micdadei in a dose‑dependent way, and bacteria grown with choline are more vulnerable to LL‑37.
- The peptide’s disruption of bacterial membranes depends on the amount of phosphatidylcholine present.
Practical Outcomes
- While the findings suggest that higher dietary choline could make some bacteria more susceptible to our innate peptide LL‑37, there’s no direct way to use LL‑37 as a supplement. Supporting the body’s own LL‑37 production (e.g., through vitamin D, adequate sleep, and gut health) remains the practical route for biohackers interested in antimicrobial defense.
Summary
The study shows that the human antimicrobial peptide LL‑37 can kill the pneumonia‑causing bacteria Legionella micdadei, and that when the bacteria are grown with extra choline (a nutrient found in many foods), they become even more sensitive to LL‑37 because their membrane changes. This reveals a link between bacterial membrane makeup and how well our natural defenses work, but it doesn’t give a ready‑to‑use supplement or treatment plan for most people.
Abstract
Legionella micdadei is responsible for community- or nosocomial-acquired pneumonia as well as the influenza-like illness Pontiac fever. The aim of this study was to investigate the ability of L. micdadei to utilize extracellular choline for phosphatidylcholine (PC) synthesis and its consequences for the phospholipid composition of its membrane system and the interaction with the human LL-37 peptide. Comparative analysis of the PC content using isotopic labeling revealed that in presence of exogenous choline 98% of the total PC was synthesized via the Pcs pathway while the remaining 2% were generated via the PE-methylation (PmtA) pathway. PC species were to a greater extent defined by the Pcs pathway in the outer membrane than in the inner membrane. While no major changes in the bacterial lipid content were observed using <sup>31</sup>P NMR, indication for utilization of longer acyl chains and slight increase of PG in response to choline addition was observed by a top-down lipidomics screen. The LL-37 peptide inhibited L. micdadei growth in a dose-dependent manner. Bacteria cultured with exogenous choline were more sensitive to the LL-37 peptide when compared to the standard culture condition. Our biophysical investigations show that the peptide perturbs bacterial-derived phospholipid monolayers and this interaction is dependent on the molar portion of PC. This interaction is responsible for the observed changes in the anti-L. micdadei activity of the LL-37 peptide.
Study Information
pubmed
2022
2022-02-26T00:00:00.000Z
10.1016/j.bbalip.2022.159138
12
51