Mycolactone cytotoxicity in Schwann cells could explain nerve damage in Buruli ulcer

Junichiro En; Sho Kitamoto; Akira Kawashima; Suguru Yonezawa; Yoshito Kishi; Norihisa Ishii; Masamichi Goto

doi:10.1371/journal.pntd.0005834

Mycolactone cytotoxicity in Schwann cells could explain nerve damage in Buruli ulcer

PLoS Negl Trop Dis. 2017 Aug 4;11(8):e0005834. doi: 10.1371/journal.pntd.0005834. eCollection 2017 Aug.

Authors

Junichiro En^{1

2

3}, Sho Kitamoto^{1

4}, Akira Kawashima⁵, Suguru Yonezawa¹, Yoshito Kishi⁶, Norihisa Ishii⁷, Masamichi Goto^{1

2}

Affiliations

¹ Department of Pathology, Kagoshima University, Kagoshima, Japan.
² National Sanatorium Hoshizuka-Keiaien, Kanoya, Kagoshima, Japan.
³ International University of Health and Welfare, Narita, Chiba, Japan.
⁴ Division of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
⁵ Department of Clinical Laboratory Science, Faculty of Medical Technology, Teikyo University, Itabashi, Tokyo, Japan.
⁶ Department of Chemistry and Chemical Biology, Harvard University, Boston, Massachusetts, United States of America.
⁷ Leprosy Research Center, National Institute of Infectious Diseases, Higashimurayama, Tokyo, Japan.

Abstract

Buruli ulcer is a chronic painless skin disease caused by Mycobacterium ulcerans. The local nerve damage induced by M. ulcerans invasion is similar to the nerve damage evoked by the injection of mycolactone in a Buruli ulcer mouse model. In order to elucidate the mechanism of this nerve damage, we tested and compared the cytotoxic effect of synthetic mycolactone A/B on cultured Schwann cells, fibroblasts and macrophages. Mycolactone induced much higher cell death and apoptosis in Schwann cell line SW10 than in fibroblast line L929. These results suggest that mycolactone is a key substance in the production of nerve damage of Buruli ulcer.

MeSH terms

Animals
Apoptosis / drug effects*
Bacterial Toxins / administration & dosage
Bacterial Toxins / toxicity*
Buruli Ulcer / microbiology
Buruli Ulcer / pathology*
Cell Line
Fibroblasts / microbiology
Fibroblasts / pathology*
Macrolides / administration & dosage
Macrolides / toxicity*
Mice
Mycobacterium ulcerans
Schwann Cells / microbiology
Schwann Cells / pathology*

Substances

Bacterial Toxins
Macrolides
mycolactone

Grants and funding

This work was supported by Japan Society for the Promotion of Science (JSPS) Grants-in-Aid for Scientific Research (KAKENHI), Grant Number is 15K08466 and URL is https://www.jsps.go.jp/english/e-grants/. MG This work was supported by the Research Program on Emerging and Re-emerging Infectious Diseases from Japan Agency for Medical Research and Development (AMED), Grant Number is 15fk0108003h0001 and URL is http://www.amed.go.jp/. NI This work was supported by Ohyama Health Foundation and URL is http://ohfin.com/about/overview. JE The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.