antibacterial protein ll-37 amide (human)

Description

LL-37, also known as hCAP18, belongs to the cathelicidins family of antimicrobial peptides that possess strong antimicrobial activity across multiple species. In humans, this is the only cathelicidin present, and it is produced in epithelial cells through the proteolytic cleavage of the hCAP-18 protein. In addition to its antimicrobial properties, LL-37 also plays a crucial role in regulating the immune system. It can inhibit inflammatory responses by suppressing the activation of TLR2 and TLR4, which recognize different components of bacterial cell walls.

Chemical properties

LL-37, a human antimicrobial peptide, is a white to off-white solid. This 37-residue peptide of cathelicidin origin is amphipathic and exhibits a broad spectrum of antimicrobial activity.

The Uses of antibacterial protein ll-37 amide (human)

LL-37 is a human antimicrobial peptide of the cathelicidin family and corresponds to the 134-170 segment of human cationic antimicrobial protein 18 (hCAP18). It plays an important role in the first line of defense against local infection and systemic invasion of pathogens at sites of inflammation and wounds. Cytotoxic to both bacterial and normal eukaryotic cells, LL-37 is significantly resistant to proteolytic degradation in solution.

Origin

LL-37 has been extensively studied since its discovery in 1995. This substance is a host defense peptide released by hCAP18 which is the only human cathelicidin.

Biological Functions

LL-37 has moderate antimicrobial activities against numerous Gram-negative and Gram-positive bacteria, including pathogens from the Pseudomonas, Escherichia, Staphylococcus, and Enterococcus genera. LL-37 is able to kill bacteria through direct antibacterial activities, as well as through immunomodulation. Like other AMPs, the primary mechanism of action is membrane disruption. The net positive charge of +6 allows for LL-37 to bind to the negatively charged membrane of bacteria. Upon binding, the introduction of transmembrane pores causes a disruption of cell integrity that leads to cell lysis and death. In addition, LL-37 is able to permeate the cell membrane in order to interact with intracellular targets, such as acyl carrier proteins. LL-37 has additional immunomodulatory properties, including both pro-inflammatory and anti-inflammatory responses, that are important for the indirect killing of bacteria For example, LL-37 is capable of inducing cell migration, proliferation and differentiation[5].

Biological Activity

The human cathelicidin HDP, LL-37, an amphipathic α-helical peptide, had a quite medium-sensitive antimicrobial activity and, unusually, the capacity to adopt this structure also in aqueous solutions at physiological salt concentrations. Most other helical AMPs only do so in the presence of biological membranes. It also had a significant capacity as a chemotactic agent for different types of immune cells, could stimulate release of pro-inflammatory chemokines and cytokines, could repress the effects of pathogen associated molecular patterns (PAMPs) such as LPS and LTA and could stimulate propagation of some cells involved in healing processes— it was a truly pleiotropic host defence peptide[6].

References

[1] Singh et al., (2014) LL-37 Peptide Enhancement of Signal Transduction by Toll-like Receptor 3 Is Regulated by pH. J. Biol. Chem. 289(40) 27614 PMID: 25092290.
[2] Tripathi et al., (2014) LL-37 modulates human neutrophil responses to influenza A virus. J. Leukoc. Biol. 96(5) 931 PMID: 25082153.
[3] Roth et al., (2020). LL-37 fights SARS-CoV-2: The Vitamin D-Inducible Peptide LL-37 Inhibits Binding of SARS-CoV-2 Spike Protein to its Cellular Receptor Angiotensin Converting Enzyme 2 In Vitro. [4] Preprint. doi: 10.1101/2020.12.02.408153
[5] Ridyard K, et al. The Potential of Human Peptide LL-37 as an Antimicrobial and Anti-Biofilm Agent. Antibiotics, 2021; 10: 650.
[6] Xhindoli D, et al. The human cathelicidin LL-37 — A pore-forming antibacterial peptide and host-cell modulator. Biochimica et Biophysica Acta (BBA) - Biomembranes, 2015; 1858: 546-566.