Earthworm-Derived Pore-Forming Toxin Lysenin and Screening of Its Inhibitors

Neelanun Sukumwang,Kazuo Umezawa

doi:10.3390/toxins5081392

Neelanun Sukumwang, Kazuo Umezawa

Open Access

https://doi.org/10.3390/toxins5081392

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Journal: Toxins	Publication Date: Aug 8, 2013
Citations: 44	License type: CC BY 4.0

Affiliation: Aichi Medical University, Keio University

Abstract

Lysenin is a pore-forming toxin from the coelomic fluid of earthworm Eisenia foetida. This protein specifically binds to sphingomyelin and induces erythrocyte lysis. Lysenin consists of 297 amino acids with a molecular weight of 41 kDa. We screened for cellular signal transduction inhibitors of low molecular weight from microorganisms and plants. The purpose of the screening was to study the mechanism of diseases using the obtained inhibitors and to develop new chemotherapeutic agents acting in the new mechanism. Therefore, our aim was to screen for inhibitors of Lysenin-induced hemolysis from plant extracts and microbial culture filtrates. As a result, we isolated all-E-lutein from an extract of Dalbergia latifolia leaves. All-E-lutein is likely to inhibit the process of Lysenin-membrane binding and/or oligomer formation rather than pore formation. Additionally, we isolated tyrosylproline anhydride from the culture filtrate of Streptomyces as an inhibitor of Lysenin-induced hemolysis.

Highlights

Pore-forming toxins are mainly produced as soluble proteins
Sticholysin I and II secreted from Stichodactyla helianthus, cytolysin from Vibrio cholerae, pleurotolysin from the Pleurotus ostreatus mushroom, Lysenin from the earthworm Eisenia foetida, all prefer sphingomyelin-containing membrane to form pores [8]
Lysenin is a pore-forming toxin existing in the coelomic fluid of the earthworm Eisenia foetida

Summary

Introduction

Pore-forming toxins are mainly produced as soluble proteins. The pore-forming toxins typically transform from soluble, monomeric proteins to oligomers that form transmembrane channels. The monomeric form of the toxin is bound to the membrane where its oligomerization is induced This process generates stable target membrane insertion, resulting in the transmembrane pore formation. This effect depends on the concentrations of toxins and the distance from the site of production [1]. Sticholysin I and II secreted from Stichodactyla helianthus, cytolysin from Vibrio cholerae, pleurotolysin from the Pleurotus ostreatus mushroom, Lysenin from the earthworm Eisenia foetida, all prefer sphingomyelin-containing membrane to form pores [8]. Lysenin is a hemolytic protein derived from the coelomic fluid of the Eisenia foetida earthworm This protein is known to bind sphingomyelin and induce lysis of erythrocytes. We have aimed at screening inhibitors of Lysenin-induced hemolysis from plant extracts and microbial culture filtrates

Structure of Lysenin and Induction of Hemolysis

Pore formation

Isolation of All-E-Lutein as an Inhibitor of Lysenin-Induced Hemolysis

Lysenin-Induced Hemolysis and the Effect of All-E-Lutein

Findings

Conclusions