Interaction between tachyplesin I, an antimicrobial peptide derived from horseshoe crab, and lipopolysaccharide

Abstract

Lipopolysaccharide (LPS) is a major constituent of the outer membrane of Gram-negative bacteria and is the very first site of interactions with antimicrobial peptides (AMPs). In order to gain better insight into the interaction between LPS and AMPs, we determined the structure of tachyplesin I (TP I), an antimicrobial peptide derived from horseshoe crab, in its bound state with LPS and proposed the complex structure of TP I and LPS using a docking program.CD and NMR measurements revealed that binding to LPS slightly extends the two β-strands of TP I and stabilizes the whole structure of TP I. The fluorescence wavelength of an intrinsic tryptophan of TP I and fluorescence quenching in the presence or absence of LPS indicated that a tryptophan residue is incorporated into the hydrophobic environment of LPS. Finally, we succeeded in proposing a structural model for the complex of TP I and LPS by using a docking program. The calculated model structure suggested that the cationic residues of TP I interact with phosphate groups and saccharides of LPS, whereas hydrophobic residues interact with the acyl chains of LPS.

Experimental Induction of Bacterial Resistance to the Antimicrobial Peptide Tachyplesin I and Investigation of the Resistance Mechanisms

“…With potent and broad-spectrum activity against both Gram-positive and Gram-negative bacteria, tachyplesin I was a promising candidate for development of antiinfection, antitumor, and antivirus drugs. Previous studies showed that tachyplesin I can kill bacteria by permeabilizing the bacterial membrane and acting on intracellular targets in bacteria to inhibit DNA, RNA, and protein synthesis and enzyme activity (11)(12)(13). Tachyplesin I acts similarly to magainin-2, MSI-78, and LL-37 by forming a toroidal transmembrane pore (14).…”

Exploring the global animal biodiversity in the search for new drugs – Spiders, scorpions, horseshoe crabs, sea spiders, centipedes, and millipedes

“…Due to their small size, positive net charge, and amphiphatic character, they are able to insert into bacterial membranes and to interact with the negatively charged lipopolysaccharides in bacterial membranes [160][161][162]164] such as lipopolysaccharides [166]. This probably leads to permeabilization and disruption of bacterial plasma membranes [166,167]. More recent studies confirmed the antibacterial activity of tachyplasins [168,169] and showed that these compounds also exhibit antiviral [170], antiparasitic [171], and anticancer effects [172].…”

“…Indeed, these compounds were found to inhibit the growth of both Gram-negative and -positive bacteria at low concentrations [161,164,165]. Due to their small size, positive net charge, and amphiphatic character, they are able to insert into bacterial membranes and to interact with the negatively charged lipopolysaccharides in bacterial membranes [160][161][162]164] such as lipopolysaccharides [166]. This probably leads to permeabilization and disruption of bacterial plasma membranes [166,167].…”

Structure-Dependent Immune Modulatory Activity of Protegrin-1 Analogs

“…In particular, a parallel emerges with the fish defense peptides, pardaxins, where adaptive changes in the overall peptide shape enable binding to lipid A head groups as well as to hydrophobic fatty acyl chains [78]. A similar pattern of interaction was also observed between LPS and the horseshoe crab major AMP, tachyplesin 1 [79]. …”