Special Issue "Pore-Forming Toxins"

Guest Editor
Prof. Dr. Shin-ichi Miyoshi
Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University 1-1-1, Tsushima-Naka, Kita-Ku, Okayama-City, Okayama 700-8530, Japan
Website: http://www.pharm.okayama-u.ac.jp/en/department/miyoshi.html
E-Mail: miyoshi@pharm.okayama-u.ac.jp
Phone: +81 86 251 7966
Fax: +81 86 251 7926
Interests: bacterial protein toxins; pore-forming toxins; cell membrane proteins/receptors; proteolytic enzymes

Dear Colleagues,

Pore-forming toxins (PFTs) are extracellular proteins that contribute to virulence of a variety of pathogenic bacteria. The PFTs are generally cytotoxic/cytolytic because they create unregulated small pores or channels in the plasma membrane of target cells. In addition, the toxins often disturb the signal pathways of the target cells via the non-lytic membrane damage, which may result in confusion of the cell functions or triggering the apoptotic cascade. Some animal toxins, such as melittin from a honeybee, a-latorotoxin from spider venoms, and cytolysins from sea anemones, are also categorized into this toxin group. The PFTs can be divided into two subgroups based on the type of pore-forming structures, namely, a-pore-forming toxins and b-pore-forming toxins. This special issue deals with various aspects of PFTs, which include biochemical and pathological properties, crystal structures of the pores created, the molecular mechanism of the toxic actions, and the development of inhibitors or antagonists to prevent the toxic actions.

Prof. Dr. Shin-ichi Miyoshi
Guest Editor

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on theInstructions for Authors page. Toxins is an international peer-reviewed Open Access monthly journal published by MDPI.

• cytolysin
• hemolysin
• leukocidin
• melittin
• membrane-damaging
• pore-forming
• toxin oligomer
• pore structure

Type of Paper: Article
Title: Multiple Vesicle Transformations That Are Induced by Melittin
Authors: Tomoyoshi Takahashi ¹, Fumimasa Nomura ², Yasunori Yokoyama ³, Yohko Tanaka-Takiguchi ^1,4, Michio Homma ¹ and Kingo Takiguchi ^1,4
Affiliations: ¹ Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya 464-8602, Japan; E-Mail: j46037a@cc.nagoya-u.ac.jp
² Department of Biomedical Information, Division of Biosystems, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda, Tokyo 101-0062, Japan
³ Department of Applied Physics, Graduate School of Engineering, Nagoya University, Chikusa-ku, Nagoya 464-8603, Japan
⁴ Structural Biology Research Center, Nagoya University, Chikusa-ku, Nagoya 464-8601, Japan
Abstract: Since melittin induces various reactions to membranes, it has been numerously studied as a model of membrane-interacting peptide. However, mechanism that melittin induces a variety of changes in the membranes is still unclear. Here we monitored melittin-induced changes in individual giant unilamellar liposomes using direct real-time imaging with dark-field optical microscope. Liposome behavior monitored was compared to results obtained by circular dichroism, cosedimentation, fluorescence quenching of tryptophan residue, and electron microscopy. Depending on the concentration of negatively charged phospholipids in membrane and the molecular ratio between lipid and melittin, melittin induced ‘Increasing Membrane Area’, ‘Phased Shrinkage’, or ‘Solubilization’ of liposomes. In Phased Shrinkage, liposomes showed formation of small particles on surface and rapid shrinking. Secondary structure of melittin was estimated as α-helix, β-sheet-like structures, or random coil for condition where Increasing Membrane Area, Phase d Shrinkage, or Solubilization is observed, respectively. When Increasing Membrane Area or Phased Shrinkage occurred, almost all melittin was bound to the membranes, and melittin reached more hydrophobic regions in compare with the case of Solubilization. These results indicate that a variety of effects of melittin is due to that melittin can take various structures and membrane-binding states depending on the conditions.

Type of Paper: Review
Title: Earthworm-Derived Pore-Forming Toxin Lysenin and Screening of Its Inhibitors
Authors: Neelanun Skumwang ¹ and Kazuo Umezawa ²
Affiliations: ¹ Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Japan; ² Department of Molecular Target Screening, Aichi Medical University School of Medicine, Japan; E-Mail: umezawa@aichi-med-u.ac.jp
Abstract: Lysenin is a novel hemolytic protein existing in the coelomic fluid of earthworm Eisenia foetida. This protein specifically binds to sphingomyelin and induces erythrocyte lysis. Lysenin is a pore-forming toxin having 41 kDa in size. Originally, this 297 amino acid protein was found to induce contraction of rat vascular smooth muscle. Lysenin induces hemolysis and is toxic to vertebrate spermatozoa, cultured mammalian cells such as normal spleen cells, colon cancer cells, and breast cancer cells, and amphibian larvae. Lysenin-induced hemolysis occurs in temperature-dependent and dose-dependent manner. The content of sphingomyelin in the membrane also affects the hemolysis induced by lysenin. Lysenin contains six tryptophan residues in which five of them are conserved in lysenin-related protein-1 and lysenin-related protein-2. It ha been suggested that these conserved tryptophans would be important for the recognition of sphingomyelin and hemolytic activity. However, precise mechanism underlying lysenin-induced hemolysis has not been elucidated. We have been screening of cellular signal transduction inhibitors of low molecular weight from microorganisms and plants. The purpose of screening is to study the mechanism of diseases using the obtained inhibitors and to develop new chemotherapeutic agents acting with new mechanism. Inhibitors of lysenin-induced hemolysis may be useful as anti-inflammatory agent. Therefore, we have aimed at screening of inhibitors of lysenin-induced hemolysis from plant extracts and microbial culture filtrates. As a result, we found the inhibitory activity in the extract of Dalbergia latifolia leaves. Dalbergia latifolia was collected in Thailand. After the extraction and purification, the active compound was identified by ESI-MS, ¹H, ¹³C and 2D-NMR. Then the purified compound was identified as all-E-lutein. In conclusion, an inhibitor of lysenin-induced hemolysis was successfully isolated from Dalbergia latifolia leaves, and the compound was identified as all-E-lutein.